Researcher Database

Osamu Ichii
Faculty of Veterinary Medicine Veterinary Medicine Basic Veterinary Sciences
Associate Professor

Researcher Profile and Settings


  • Faculty of Veterinary Medicine Veterinary Medicine Basic Veterinary Sciences

Job Title

  • Associate Professor


  • D.V.M.Ph.D.(Hokkaido University)


Research funding number

  • 60547769

J-Global ID

Research Interests

  • CKD   Autoimmune disease   Renal pathology   IL-36   Podocyte injury   レーザーマイクロダイセクション   電子顕微鏡   腎生検   exosome   尿   biomarker   慢性腎臓病   microRNA   モデルマウス   伴侶動物   疾患モデルマウス   慢性糸球体腎炎   犬   腎疾患   猫   マウス   ネコ   イヌ   糸球体   自己免疫   miRNA   腎臓   分子形態学   獣医解剖学   Veterinary Nephrology and Urology   Molecular Morphology   Veterinary Anatomy   

Research Areas

  • Life sciences / Nephrology
  • Life sciences / Anatomy
  • Life sciences / Veterinary medicine
  • Life sciences / Veterinary medicine
  • Life sciences / Veterinary medicine
  • Life sciences / Laboratory animal science
  • Life sciences / Animals: biochemistry, physiology, behavioral science

Academic & Professional Experience

  • 2017/04 - Today Faculty of Veterinary Medicine, Hokkaido University Division of Basic Veterinary Science, Laboratory of Anatomy Associate professor
  • 2014/04 - 2017/03 Hokkaido University Graduate school of veterinary medicine Associate professor
  • 2009/04 - 2014/03 Hokkaido University Graduate School of Veterinary Medicine
  • 2011/09 - 2012/08 NIH NIDDK 腎臓病研究部門 リサーチフェロー
  • 2007/04 - 2009/03 Hokkaido University Graduate School of Veterinary Medicine
  • 2007 - 2009 Postdoctoral Fellowships of Japan Society for the Promotion of Science,Graduate School of Veterinary Medicine Veterinary Medicine Department of Biomedical Sciences Laboratory of Anatomy


  •        - 2009  Hokkaido University  Graduate School of Veterinary Medicine  Veterinary Medicine
  •        - 2009  Hokkaido University  Graduate School, Division of Veterinary Medicine  Veterinary Medicine
  •        - 2006  Kagoshima University  Faculty of Agriculture  Veterinary Medicine
  •        - 2006  Kagoshima University  Faculty of Agriculture  Department of Veterinary Medicine

Association Memberships

  • 日本解剖学会   日本獣医腎泌尿器学会   日本獣医学会   Japanese Association for Laboratory Animal Science   Japanese Association of Anatomists   Japanese Association Veterinary Nephrology and Urology   Japanease Society of Veterinary Science   

Research Activities

Published Papers

  • El-Naseery NI, Elewa YHA, Ichii O, Kon Y
    Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 220 9 - 20 0940-9602 2018/11 [Refereed][Not invited]
  • Terazawa T, Nishimura T, Mitani T, Ichii O, Ikeda T, Kosenda K, Tatsumi E, Nakayama Y
    Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs 21 (3) 387 - 391 1434-7229 2018/09 [Refereed][Not invited]
  • Ichii O, Nakamura T, Horino T, Yabuki A, Elewa YHA, Kon Y
    The American journal of pathology 188 (9) 2120 - 2138 0002-9440 2018/09 [Refereed][Not invited]
  • Nakamura T, Elewa YHA, Ichii O, Hosotani M, Ghonimi WAM, Tatsumi O, Nagasaki KI, Kon Y
    The Journal of veterinary medical science 80 (9) 1368 - 1372 0916-7250 2018/09 [Refereed][Not invited]
  • Kamikawa A, Sakazaki J, Ichii O
    Biochemical and biophysical research communications 503 (3) 1710 - 1715 0006-291X 2018/09 [Refereed][Not invited]
  • Horino T, Ichii O, Asagiri T, Eguchi T, Terada Y
    QJM : monthly journal of the Association of Physicians 1460-2725 2018/09 [Refereed][Not invited]
  • Nakamura T, Ichii O, Irie T, Kouguchi H, Sotozaki K, Chihara M, Sunden Y, Nagasaki KI, Tatsumi O, Elewa YHA, Kon Y
    Cell and tissue research 0302-766X 2018/08 [Refereed][Not invited]
  • Masum MA, Ichii O, Elewa YHA, Nakamura T, Otani Y, Hosotani M, Kon Y
    Scientific reports 8 (1) 10276  2018/07 [Refereed][Not invited]
  • Nakayama Y, Oshima N, Tatsumi E, Ichii O, Nishimura T
    Hernia : the journal of hernias and abdominal wall surgery 1265-4906 2018/07 [Refereed][Not invited]
  • Islam MA, Torigoe D, Kameda Y, Irie T, Kouguchi H, Nakao R, Masum MA, Ichii O, Kon Y, Tag-El-Din-Hassan HT, Morimatsu M, Yagi K, Agui T
    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 65 65 - 71 1567-1348 2018/07 [Refereed][Not invited]
  • Aoyama-Maeda N, Horino T, Ichii O, Terada Y
    Romanian journal of internal medicine = Revue roumaine de medecine interne 56 (2) 117 - 121 1220-4749 2018/06 [Refereed][Not invited]
  • Nakamura T, Ichii O, Irie T, Mizoguchi T, Shinohara A, Kouguchi H, Sunden Y, Otsuka-Kanazawa S, Ali Elewa YH, Koshimoto C, Nagasaki KI, Kon Y
    Histology and histopathology 33 (6) 555 - 565 0213-3911 2018/06 [Refereed][Not invited]
  • Morita T, Nakamura K, Osuga T, Kobayashi A, Ichii O, Yabuki A, Takiguchi M
    The Journal of veterinary medical science 80 (6) 939 - 944 0916-7250 2018/06 [Refereed][Not invited]
  • Eguchi T, Inoue K, Horino T, Matsumoto T, Kamioka S, Nishida Y, Morimoto M, Morimoto N, Ichii O, Terada Y
    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 1076-1608 2018/06 [Refereed][Not invited]
  • Horino T, Matsumoto T, Inoue K, Ichii O, Terada Y
    CEN case reports 7 (1) 34 - 38 2018/05 [Refereed][Not invited]
  • Ishii C, Ikenaka Y, Ichii O, Nakayama SMM, Nishimura SI, Ohashi T, Tanaka M, Mizukawa H, Ishizuka M
    Poultry science 97 (5) 1722 - 1729 0032-5791 2018/05 [Refereed][Not invited]
  • Horino T, Hatakeyama Y, Ichii O, Matsumoto T, Shimamura Y, Inoue K, Terada Y, Okuhara Y
    Clinical and experimental nephrology 22 (2) 337 - 345 1342-1751 2018/04 [Refereed][Not invited]
  • Horino T, Osakabe Y, Matsuura M, Ichii O, Terada Y
    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 24 (3) 159 - 164 1076-1608 2018/04 [Refereed][Not invited]
  • Horino T, Ichii O, Shimamura Y, Terada Y
    Nephrology (Carlton, Vic.) 23 (4) 378 - 379 1320-5358 2018/04 [Refereed][Not invited]
  • Nakamura R, Yabuki A, Ichii O, Mizukawa H, Yokoyama N, Yamato O
    Journal of comparative pathology 160 79 - 83 0021-9975 2018/04 [Refereed][Not invited]
  • Horino T, Matsumoto T, Inoue K, Ichii O, Terada Y
    Joint, bone, spine : revue du rhumatisme 85 (2) 243 - 245 1297-319X 2018/03 [Refereed][Not invited]
  • Ichii O, Nakamura T, Irie T, Kouguchi H, Sotozaki K, Horino T, Sunden Y, Elewa YHA, Kon Y
    Experimental biology and medicine (Maywood, N.J.) 243 (5) 418 - 427 1535-3702 2018/03 [Refereed][Not invited]
  • Horino T, Matsumoto T, Inoue K, Ichii O, Terada Y
    eNeurologicalSci 10 28 - 30 2018/03 [Refereed][Not invited]
  • M. Hosotani, O. Ichii, T. Nakamura, S. O. Kanazawa, Y. Hosny Ali Elewa, Y. Kon
    LUPUS 27 (1) 82 - 94 0961-2033 2018/01 [Refereed][Not invited]
    Ovulation and oocyte-pick-up are essential processes in fertilization. Herein, we found associations between autoimmune disease and the aforementioned processes in mice. At three and six months, along with the evaluation of autoimmune disease indices, the ovary, mesosalpinx, and oviducts were histologically examined in C57BL/6, MRL/MpJ, and MRL/MpJ-Fas(lpr/lpr) mice as healthy control, mild and severe models of autoimmune disease, respectively. In superovulated mice, the number of oocyte cumulus complexes found in the ampulla was macroscopically counted, and that of ovulated oocytes was histologically evaluated, as indicated by ruptured follicles or corpora hemorrhagica in ovaries. Finally, the oocyte-pick-up rate was calculated. In MRL/MpJ-Fas(lpr/lpr) mice, the oocyte-pick-up rate decreased with disease-related deterioration, unlike in other mouse strains. Further, more ovulated oocytes were found in MRL/MpJ mice than in C57BL/6 mice, and this number significantly decreased with aging in MRL/MpJ-Fas(lpr/lpr) mice. Numerous T-cells infiltrated into the infundibulum or a part of the mesosalpinx in aged MRL/MpJ-Fas(lpr/lpr) mice, and their infundibulum showed swelling and fewer ciliated epithelial cells compared to that of C57BL/6 mice. In conclusion, the progression of severe autoimmune disease affected the oocyte-pick-up process through histopathological changes in the infundibulum. These results provide important insights into female infertility associated with autoimmune disease.
  • Ichii O, Horino T
    Journal of toxicologic pathology 31 (1) 23 - 34 0914-9198 2018/01 [Refereed][Not invited]
  • Nakamura T, Chihara M, Ichii O, Otsuka-Kanazawa S, Nagasaki KI, Elewa YHA, Tatsumi O, Kon Y
    PloS one 13 (4) e0196364  2018 [Refereed][Not invited]
  • Yamada S, Itai S, Nakamura T, Yanaka M, Saidoh N, Chang YW, Handa S, Harada H, Kagawa Y, Ichii O, Konnai S, Kaneko MK, Kato Y
    Monoclonal antibodies in immunodiagnosis and immunotherapy 36 (5) 224 - 230 2017/10 [Refereed][Not invited]
  • Osamu Ichii, Junpei Kimura, Tadashi Okamura, Taro Horino, Teppei Nakamura, Hayato Sasaki, Yaser Hosny Ali Elewa, Yasuhiro Kon
    FRONTIERS IN IMMUNOLOGY 8 1346  1664-3224 2017/10 [Refereed][Not invited]
    IL-36 alpha, a member of the IL-1 family, is a crucial mediator of inflammatory responses. We previously found that IL-36 alpha was overexpressed in injured distal tubules (DTs); however, its pathological function remains unclear. Herein, unilateral ureter obstruction (UUO) or folic acid (FA) injection was performed in mouse kidneys to assess the role of IL-36 alpha in kidney injury. IL-36 alpha mRNA and protein expression significantly increased in the kidneys within 24 h after UUO. IL-36 alpha localized to dilated DTs. IL-36 alpha expression significantly correlated with the progression of tubulointerstitial cell infiltration and tubular epithelium cell death in UUO kidneys and with renal dysfunction in FA-induced acute kidney injury mice. At 24 h after UUO, IL-36 alpha(+) DT epithelial cells showed loose intercellular digitations. IL-1RL2, an IL-36 alpha receptor protein, localized to podocytes, proximal tubules, and DTs in the healthy kidney. IL-1RL2 was expressed in interstitial cells and platelets or extended primary cilia of DT epithelial cells in UUO kidneys. IL-36 alpha stimulation promoted the production of IL-6 and Prss35, an inflammatory cytokine and collagen remodeling-associated enzyme, respectively, in cultured NIH3T3 fibroblasts. UUO-treated IL-36 alpha-knockout (KO) mice showed milder kidney injury features than wild-type (WT) mice did. In UUO kidneys from IL-36 alpha-KO mice, the expression of genes associated with inflammatory response and sensory perception was significantly different from that in WT mice. Altogether, our data indicate an association between intrarenal IL-36 alpha overexpression and the progression of tubulointerstitial inflammations and morpho-functional alterations of DT epithelial cells. IL-36 alpha may be a novel kidney injury marker useful for evaluating DT damages.
  • T. Horino, O. Ichii, K. Ode-Hamada, Y. Terada
    QJM-AN INTERNATIONAL JOURNAL OF MEDICINE 110 (9) 593 - 594 1460-2725 2017/09 [Refereed][Not invited]
  • Md Abdul Masum, Osamu Ichii, Yaser Hosny Ali Elewa, Teppei Nakamura, Yasuhiro Kon
    BMC NEPHROLOGY 18 (1) 280  1471-2369 2017/09 [Refereed][Not invited]
    Background: The renal vasculature plays important roles in both homeostasis and pathology. In this study, we examined pathological changes in the renal microvascular in mouse models of kidney diseases. Methods: Glomerular lesions (GLs) in autoimmune disease-prone male BXSB/MpJ-Yaa (Yaa) mice and tubulointerstitial lesions (TILs) in male C57BL/6 mice subjected to unilateral ureteral obstruction (UUO) for 7 days were studied. Collected kidneys were examined using histopathological techniques. A nonparametric Mann-Whitney U test (P < 0.05) was performed to compare healthy controls and the experimental mice. The Kruskal-Wallis test was used to compare three or more groups, and multiple comparisons were performed using Scheffe's method when significant differences were observed (P < 0.05). Results: Yaa mice developed severe autoimmune glomerulonephritis, and the number of CD34(+) glomerular capillaries decreased significantly in GLs compared to that in control mice. However, UUO-treated mice showed severe TILs only, and CD34(+) tubulointerstitial capillaries were decreased significantly in TILs with the progression of tubulointerstitial fibrosis compared to those in untreated control kidneys. Infiltrations of B-cells, T-cells, and macrophages increased significantly in the respective lesions of both disease models (P < 0.05). In observations of vascular corrosion casts by scanning electron microscopy and of microfil rubber-perfused thick kidney sections by fluorescence microscopy, segmental absences of capillaries were observed in the GLs and TILs of Yaa and UUO-treated mice, respectively. Further, transmission electron microscopy revealed capillary endothelial injury in the respective lesions of both models. The numbers of CD34(+) glomerular and tubulointerstitial capillaries were negatively correlated with all examined parameters in GLs (P < 0.05) and TILs (P < 0.01), respectively. Conclusions: From the analysis of mouse models, we identified inverse pathological correlations between the number of local capillaries in GLs and TILs and the severity of kidney diseases.
  • Teppei Nakamura, Naoya Karakida, Ai Dantsuka, Osamu Ichii, Yaser Hosny Ali Elewa, Yasuhiro Kon, Ken-ichi Nagasaki, Hideki Hattori, Tomoji Yoshiyasu
    JOURNAL OF VETERINARY MEDICAL SCIENCE 79 (7) 1230 - 1235 0916-7250 2017/07 [Refereed][Not invited]
    Syrian golden hamsters (Mesocricetus auratus) are useful laboratory rodents for studying human infectious diseases, metabolic diseases and cancer. In other rodents, such as mice and rats, a mixture of medetomidine, midazolam and butorphanol functions as a useful anesthetic, although it alters some blood biochemical parameters. In this study, we examined the effects of this mixture on anesthesia and blood biochemical parameters, and the action of atipamezole, a medetomidine antagonist, in hamsters. Intramuscular injection of a mixture of medetomidine, midazolam and butorphanol at doses of 0.15, 2.0 and 2.5 mg/kg, respectively, had a short induction time (within 5 min) and produced an anesthetic duration of approximately 100 min in hamsters. We also demonstrated that 0.15 mg/kg of atipamezole, corresponding to the same dose as medetomidine, made hamsters recover quickly from anesthesia. The anesthetic agent markedly altered metabolic parameters, such as plasma glucose and insulin; however, 0.15 mg/kg of atipamezole returned these levels to normal range within approximately 10 min after the injection. The anesthetic also slightly altered mineral levels, such as plasma inorganic phosphorus, calcium and sodium; the latter two were also improved by atipamezole. Our results indicated that the mixture of medetomidine, midazolam, and butorphanol at doses of 0.15, 2.0 and 2.5 mg/kg, respectively, functioned as an effective anesthetic, and atipamezole was useful for antagonizing both anesthesia and biochemical alteration in hamsters.
  • Tohru Yamamori, Tomoya Sasagawa, Osamu Ichii, Mie Hiyoshi, Tomoki Bo, Hironobu Yasui, Yasuhiro Kon, Osamu Inanami
    JOURNAL OF RADIATION RESEARCH 58 (3) 292 - 301 0449-3060 2017/05 [Refereed][Not invited]
    Mitochondria strongly contribute to the maintenance of cellular integrity through various mechanisms, including oxidative adenosine triphosphate production and calcium homeostasis regulation. Therefore, proper regulation of the abundance, distribution and activity of mitochondria is crucial for the maintenance of cellular homeostasis. Previous studies have shown that ionizing radiation (IR) alters mitochondrial functions, suggesting that mitochondria are likely to be an important target of IR. Though IR reportedly influences cellular mitochondrial abundance, the mechanism remains largely unknown. In this study, we examined how IR influences mitochondrial abundance in mouse fibroblasts. When mouse NIH/3T3 cells were exposed to X-rays, a time-dependent increase was observed in mitochondrial DNA (mtDNA) and mitochondrial mass, indicating radiation-induced upregulation of mitochondrial abundance. Meanwhile, not only did we not observe a significant change in autophagic activity after irradiation, but in addition, IR hardly influenced the expression of two mitochondrial proteins, cytochrome c oxidase subunit IV and cytochrome c, or the mRNA expression of Polg, a component of DNA polymerase gamma. We also observed that the expression of transcription factors involved in mitochondrial biogenesis was only marginally affected by IR. These data imply that radiation-induced upregulation of mitochondrial abundance is an event independent of macroautophagy and mitochondrial biogenesis. Furthermore, we found evidence that IR induced long-term cell cycle arrest and cellular senescence, indicating that these events are involved in regulating mitochondrial abundance. Considering the growing significance of mitochondria in cellular radioresponses, we believe the present study provides novel insights into understanding the effects of IR on mitochondria.
  • Yamada S, Kaneko MK, Nakamura T, Ichii O, Konnai S, Kato Y
    Monoclonal antibodies in immunodiagnosis and immunotherapy 36 (2) 77 - 79 2017/04 [Refereed][Not invited]
  • Osamu Ichii, Masataka Chihara, Shin-Hyo Lee, Teppei Nakamura, Saori Otsuka-Kanazawa, Taro Horino, Yaser Hosny Ali Elewa, Yasuhiro Kon
    AUTOIMMUNITY 50 (2) 114 - 124 0891-6934 2017/03 [Refereed][Not invited]
    Inbred MRL/MpJ mice show several unique phenotypes in tissue regeneration processes and the urogenital and immune systems. Clarifying the genetic and molecular bases of these phenotypes requires the analysis of their genetic susceptibility locus. Herein, hydronephrosis development was incidentally observed in MRL/MpJ-derived chromosome 11 (D11Mit21-212)-carrying C57BL/6N-based congenic mice, which developed bilateral or unilateral hydronephrosis in both males and females with 23.5% and 12.5% prevalence, respectively. Histopathologically, papillary malformations of the transitional epithelium in the pelvic-ureteric junction seemed to constrict the ureter luminal entrance. Characteristically, eosinophilic crystals were observed in the lumen of diseased ureters. These ureters were surrounded by infiltrating cells mainly composed of numerous CD3(+)T-cells and B220(+)B-cells. Furthermore, several Iba-1(+)macrophages, Gr-1(+)granulocytes, mast cells and chitinase 3-like 3/Ym1 (an important inflammatory lectin)-positive cells were detected. Eosinophils also accumulated to these lesions in diseased ureters. Some B6.MRL-(D11Mit21-D11Mit212) mice had duplicated ureters. We determined>100 single nucleotide variants between C57BL/6N- and MRL/MpJ-type chromosome 11 congenic regions, which were associated with nonsynonymous substitution, frameshift or stopgain of coding proteins. In conclusion, B6.MRL-(D11Mit21-D11Mit212) mice spontaneously developed hydronephrosis due to obstructive uropathy with inflammation. Thus, this mouse line would be useful for molecular pathological analysis of obstructive uropathy in experimental medicine.
  • N. Yokoyama, H. Ohta, J. Yamazaki, Y. Kagawa, O. Ichii, N. Khoirun, T. Morita, T. Osuga, S. Y. Lim, N. Sasaki, K. Morishita, K. Nakamura, M. Takiguchi
    JOURNAL OF COMPARATIVE PATHOLOGY 156 (2-3) 183 - 190 0021-9975 2017/02 [Refereed][Not invited]
    Inflammatory colorectal polyps (ICRPs) are characterized by the formation of multiple or solitary polyps with marked neutrophil infiltration in the colorectal area, and are speculated to be a novel form of breed-specific canine idiopathic inflammatory bowel disease (IBD). In human IBD, toll-like receptor (TLR) 2 and TLR4 have been reported to be involved in the pathogenesis of the disease. The aim of this study was to evaluate the expression of TLR2 and TLR4 mRNA in the colorectal mucosa of dogs with ICRPs by in-situ hybridization using an RNAscope assay. Samples of inflamed colorectal mucosa (n = 5) and non-inflamed mucosa (n = 5) from miniature dachshunds (MDs) with ICRPs and colonic mucosa from healthy beagles (n = 5) were examined. TLR2 and TLR4 hybridization signals were localized to the colorectal epithelium, inflammatory cells and fibroblasts in the inflamed colorectal mucosa of affected dogs. The signals were significantly greater in inflamed colorectal epithelium compared with non-inflamed epithelium of MDs with ICRPs and healthy beagles (P <0.05). These results suggest that increased expression of TLR2 and TLR4 mRNA in the inflamed colorectal mucosa results from not only inflammatory cell infiltration, but also the upregulation of TLR2 and TLR4 mRNA in the colonic epithelium. (C) 2016 Elsevier Ltd. All rights reserved.
  • Osamu Ichii, Hiroshi Ohta, Taro Horino, Teppei Nakamura, Marina Hosotani, Tatsuya Mizoguchi, Keitaro Morishita, Kensuke Nakamura, Yuki Hoshino, Satoshi Takagi, Noboru Sasaki, Mitsuyoshi Takiguchi, Ryo Sato, Kazuhisa Oyamada, Yasuhiro Kon
    SCIENTIFIC REPORTS 7 40340  2045-2322 2017/01 [Refereed][Not invited]
    MicroRNAs act as post-transcriptional regulators, and urinary exosome (UExo)-derived microRNAs may be used as biomarkers. Herein, we screened for UExo-derived microRNAs reflecting kidney disease (KD) status in dogs. Examined dogs were divided into healthy kidney control (HC) and KD groups according to renal dysfunction. We confirmed the appearance of UExo having irregular globe-shapes in a dog by immunoblot detection of the exosome markers, TSG101 and CD9. Based on our previous data using KD model mice and the data obtained herein by next generation sequencing of UExo-derived microRNAs in dogs, miR-26a, miR-146a, miR-486, miR-21a, and miR-10a/b were selected as candidate microRNAs. In particular, UExo-derived miR-26a and miR-10a/b were significantly decreased in KD dogs, and miR-26a levels negatively correlated with deteriorated renal function compared to the other miRNAs. UExo-derived miR-21a levels corrected or not to that of internal control microRNAs in UExo, miR-26a and miR-191, significantly increased with renal dysfunction. In kidney tissues, the decrease of miR-26a and miR-10a/ b in the glomerulus and miR-10b in the tubulointerstitium negatively correlated with deteriorated renal function and histopathology. Increased miR-21a in the tubulointerstitium rather than in the glomerulus correlated with deteriorated renal histopathology. In conclusion, microRNAs reflecting the changes in renal function and histopathology in dogs were identified in this study.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon
    AUTOIMMUNITY 50 (5) 306 - 316 0891-6934 2017 [Refereed][Not invited]
    MRL/MpJ-Fas(lpr) (lpr) mice are a model for autoimmune diseases such as systemic lupus erythematosus (SLE). These diseases mainly affect women, with a 10:1 female-to-male ratio, and cause pleuropulmonary lesions. We previously revealed a correlation between mediastinal fat-associated lymphoid cluster (MFALC) development and cellular infiltration in the lungs of lpr male mice; however, we did not report on MFALCs in females. The purpose of this investigation was to reveal sex-related differences in MFALCs in lpr mice. We compared the morphological features of MFALCs and lung mononuclear cell aggregates (LMCAs) in 5-month-old male and female lpr mice. The females showed significantly elevated anti-dsDNA autoantibody titers and larger MFALCs, with a higher ratio of lymphatic vessel (LV) and high endothelial venule (HEV) areas to MFALC area, and greater numbers of T- and B-cells, macrophages, and proliferating and dendritic cells in MFALCs and LMCAs than males. Our data indicated that MFALCs were more developed and lung lesions were more severe in female than in male lpr mice, thereby suggesting a potential role for LVs and HEVs in the establishment of MFALCs and lung lesions. Further investigation in female lpr mice will be needed for treatment of human respiratory diseases and autoimmune disorders.
  • T. Horino, T. Matsumoto, Y. Terada, O. Ichii
    QJM-AN INTERNATIONAL JOURNAL OF MEDICINE 109 (12) 827 - 828 1460-2725 2016/12 [Refereed][Not invited]
  • Akira Yabuki, Akiko Miyazaki, Osamu Ichii, Moeko Kohyama, Mariko Sawa, Osamu Yamato
    RESEARCH IN VETERINARY SCIENCE 109 71 - 73 0034-5288 2016/12 [Refereed][Not invited]
    Chronic kidney disease (CKD) often results in end-stage renal failure in young dogs; however, the pathogenesis of this disease is not established. This study investigated renal expression of cyclooxygenase (COX)-1 and COX-2 proteins in three dogs with chronic kidney disease by immunohistochemistry. Histopathology showed asynchronous differentiation of renal tissues, including immature glomeruli. COX-1 signals were not detected in diseased or normal kidneys. COX-2 signals were low or undetectable in diseased kidneys, while normal kidneys showed clear positive signals in the macula densa (MD). Quantitative scores of COX-2 in diseased kidneys were significantly lower than those in normal kidneys. These findings demonstrate low renal COX-2 expression in CKD in young dogs, but whether this is correlated with disease pathogenesis remains unclear. (C) 2016 Elsevier Ltd. All rights reserved.
  • Horino T, Ichii O, Hamada-Ode K, Matsumoto T, Shimamura Y, Inoue K, Terada Y
    Molecular and clinical oncology 5 (6) 693 - 696 2049-9450 2016/12 [Refereed][Not invited]
  • Akihiro Kamikawa, Osamu Ichii, Junpei Sakazaki, Toru Ishikawa
    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY 311 (5) C808 - C819 0363-6143 2016/11 [Refereed][Not invited]
    The Cl- secretion via Ca2+-activated Cl- channel (CaCC) is critical for fluid secretion in exocrine glands like the salivary gland. Also in the mammary gland, it has been hypothesized that CaCC plays an important role in the secretion of Cl- and aqueous phase of milk. However, there has been no evidence for the functional expression of CaCC in native mammary secretory (MS) cells of lactating animals. We therefore assessed membrane current in MS cells that were freshly isolated from lactating mice using whole cell patch-clamp techniques. In MS cells, we detected CaCC current that exhibited the following characteristics: 1) Ca2+-dependent activation at the concentrations of sub-micromolar range; 2) voltage-dependent activation; 3) slow kinetics for activation and deactivation; 4) outward rectification of the steady-state current; 5) anion permeability in the sequence of I- > NO3- > Br- > Cl- >> glutamate; 6) inhibition by Cl- channel blockers (niflumic acid, DIDS, and CaCCinh-A01). These characteristics of native CaCC current were similar to reported characteristics of heterologously expressed TMEM16A. RT-PCR analyses showed the expression of multiple CaCC channels including TMEM16A, Best1, and Best3 in the mammary glands of lactating mice. Immuno-histochemical staining revealed the localization of TMEM16A protein at the apical membrane of the MS cells. Collectively, our data strongly suggest that MS cells functionally express CaCC, which is at least partly constituted by TMEM16A. The CaCC such as TMEM16A at the apical membrane of the MS cells may influence the quantity and/ or quality of milk.
  • Maiko Ono, Hayato Sasaki, Kenichi Nagasaki, Daisuke Torigoe, Osamu Ichii, Nobuya Sasaki, Takashi Agui
    JAPANESE JOURNAL OF VETERINARY RESEARCH 64 (4) 265 - 271 0047-1917 2016/11 [Refereed][Not invited]
    The three different mouse handling methods, picking up by tails, tunnels, and open hands were performed using the ICGN glomerulonephritis mouse and the severity of symptoms was evaluated. The handling groups exhibited a tendency of more severe symptoms than the non-handling control group. Female mice handled by their tails showed significantly more severe symptoms than the control group. In addition, we subjected the normal laboratory mice, C57BL/6 and BALB/c mice to tail and tunnel handling to assess the stress conditions. The plasma corticosterone level in the tail-handled mice was higher than that in control mice. These results indicate that handling causes stress and may affect the phenotype of disease model mice.
  • Teppei Nakamura, Osamu Ichii, Takao Irie, Marina Hosotani, Ai Dantsuka, Saori Nakamura, Shinobu Sato, Kozue Sotozaki, Hirokazu Kouguchi, Tomoji Yoshiyasu, Ken-ichi Nagasaki, Yasuhiro Kon
    JAPANESE JOURNAL OF VETERINARY RESEARCH 64 (4) 273 - 276 0047-1917 2016/11 [Refereed][Not invited]
    The cotton rat (Sigmodon hispidus) is a laboratory rodent used for studying human infectious diseases. However, a lack of suitable anesthetic agents inconveniences the use of cotton rats in surgical manipulation. This study demonstrated that subcutaneous injection of the mixture of medetomidine, midazolam, and butorphanol (0.15, 2.0, and 2.5 mg/kg, respectively), which is a suitable anesthetic agents for mice and rats, produced an anesthetic duration of more than 50 min in cotton rats. We also demonstrated that 0.15 mg/kg of atipamezole, an antagonist of medetomidine, produced a quick recovery from anesthesia in cotton rats. This indicated that the anesthetic mixture of medetomidine, midazolam, and butorphanol, functioned as a useful and effective anesthetic for short-term surgery in cotton rats.
  • Teppei Ikeda, Osamu Ichii, Saori Otsuka-Kanazawa, Teppei Nakamura, Yaser Hosny Ali Elewa, Yasuhiro Kon
    JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY 37 (4-5) 153 - 164 0142-4319 2016/10 [Refereed][Not invited]
    Skeletal muscle myofibers constantly undergo degeneration and regeneration. Histopathological features of 6 skeletal muscles (cranial tibial [CT], gastrocnemius, quadriceps femoris, triceps brachii [TB], lumbar longissimus muscles, and costal part of the diaphragm [CPD]) were compared using C57BL/10ScSn-Dmd (mdx) (mdx) mice, a model for muscular dystrophy versus control, C57BL/10 mice. Body weight and skeletal muscle mass were lower in mdx mice than the control at 4 weeks of age; these results were similar at 6-30 weeks. Additionally, muscular lesions were observed in all examined skeletal muscles in mdx mice after 4 weeks, but none were noted in the controls. Immunohistochemical staining revealed numerous paired box 7-positive satellite cells surrounding the embryonic myosin heavy chain-positive regenerating myofibers, while the number of the former and staining intensity of the latter decreased as myofiber regeneration progressed. Persistent muscular lesions were observed in skeletal muscles of mdx mice between 4 and 14 weeks of age, and normal myofibers decreased with age. Number of muscular lesions was lowest in CPD at all ages examined, while the ratio of normal myofibers was lowest in TB at 6 weeks. In CT, TB, and CPD, Iba1-positive macrophages, the main inflammatory cells in skeletal muscle lesions, showed a significant positive correlation with the appearance of regenerating myofibers. Additionally, B220-positive B-cells showed positive and negative correlation with regenerating and regenerated myofibers, respectively. Our data suggest that degenerative and regenerative features of myofibers differ among skeletal muscles and that inflammatory cells are strongly associated with regenerative features of myofibers in mdx mice.
  • Truc Quynh Thai, Huy Bang Nguyen, Sei Saitoh, Bao Wu, Yurika Saitoh, Satoshi Shimo, Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon, Takashi Takaki, Kensuke Joh, Nobuhiko Ohno
    MEDICAL MOLECULAR MORPHOLOGY 49 (3) 154 - 162 1860-1480 2016/09 [Refereed][Not invited]
    Serial block-face imaging using scanning electron microscopy enables rapid observations of three-dimensional ultrastructures in a large volume of biological specimens. However, such imaging usually requires days for sample preparation to reduce charging and increase image contrast. In this study, we report a rapid procedure to acquire serial electron microscopic images within 1 day for three-dimensional analyses of subcellular ultrastructures. This procedure is based on serial block-face with two major modifications, including a new sample treatment device and direct polymerization on the rivets, to reduce the time and workload needed. The modified procedure without uranyl acetate can produce tens of embedded samples observable under serial block-face scanning electron microscopy within 1 day. The serial images obtained are similar to the block-face images acquired by common procedures, and are applicable to three-dimensional reconstructions at a subcellular resolution. Using this approach, regional immune deposits and the double contour or heterogeneous thinning of basement membranes were observed in the glomerular capillary loops of an autoimmune nephropathy model. These modifications provide options to improve the throughput of three-dimensional electron microscopic examinations, and will ultimately be beneficial for the wider application of volume imaging in life science and clinical medicine.
  • Osamu Ichii, Teppei Nakamura, Takao Irie, Hirokazu Kouguchi, Daisuke Nakamura, Saori Nakamura, Shinobu Sato, Keisuke Yokoyama, Taro Horino, Yuji Sunden, Yaser Hosny Ali Elewa, Yasuhiro Kon
    HISTOCHEMISTRY AND CELL BIOLOGY 146 (3) 351 - 362 0948-6143 2016/09 [Refereed][Not invited]
    The cotton rat (Sigmodon hispidus) is a laboratory rodent that has been used for studies on human infectious diseases. In the present study, we observed that female cotton rats, not the male cotton rats, developed chronic anemia characterized by reduced red blood cell, hemoglobin, and hematocrit levels from 5 to 9 months of age without any changes in the mean corpuscular hemoglobin and volume levels. In peripheral blood, the reticulocyte count did not increase in response to anemia in female cotton rats, and no extramedullary hematopoiesis was observed in the liver or spleen. Further, the serum levels of urea nitrogen and creatinine increased from 5 to 9 months of age in female cotton rats compared to male cotton rats, and these increases became more prominent from 10 months of age onward, indicating chronic kidney disease. Histopathologically, female cotton rats manifested tubulointerstitial lesions characterized by the infiltration of mononuclear cells, including plasma cells and CD3(+) T-cells, as well as the dilation of calbindin-D28k(+) distal tubules from 5 to 9 months of age. The severity of these lesions progressed from 10 months of age onward, and renal fibrotic features and numerous tubular cysts appeared without any obvious glomerular lesions. A significant decrease in the erythropoietin protein levels was observed in the kidney of aged female cotton rats, and significant correlations were detected between anemia and tubulointerstitial damage. These results suggest that aged female cotton rats chronically develop renal anemia, and this rodent may serve as a novel model to elucidate its pathogenesis.
  • Dugar Delgermurun, Soichiro Yamaguchi, Osamu Ichii, Yasuhiro Kon, Shigeo Ito, Ken-ichi Otsuguro
    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY 187 43 - 49 1532-0456 2016/09 [Refereed][Not invited]
    Epithelioid cells in the chicken thoracic aorta are chemoreceptor cells that release 5-HT in response to hypoxia. It is likely that these cells play a role in chemoreception similar to that of glomus cells in the carotid bodies of mammals. Recently, H2S was reported to be a key mediator of carotid glomus cell responses to hypoxia. The aim of the present study was to reveal the mechanism of action of H2S on 5-HT outflow from chemoreceptor cells in the chicken thoracic aorta. The 5-HT outflow induced by NaHS, an H2S donor, and Na2S3, a polysulfide, was measured by using a HPLC equipped with an electrochemical detector. NaHS (0.3-3 mM) caused a concentration-dependent increase in 5-HT outflow, which was significantly inhibited by the removal of extracellular Ca2+. outflow induced by NaHS (0.3 mM) was also significantly inhibited by voltage-dependent L- and N-type Ca2+ channel blockers and a selective TRPA1 channel blocker. Cinnamaldehyde, a TRPA1 agonist, mimicked the secretory response to H2S. 5-HT outflow induced by Na2S3 (10 M) was also inhibited by the TRPA1 channel blocker. Furthermore, the expression of TRPA1 was localized to 5-HT-containing chemoreceptor cells in the aortic wall. These findings suggest that the activation of TRPA1 and voltage-dependent Ca2+ channels is involved in H2S-evoked 5-HT release from chemoreceptor cells in the chicken aorta. (C) 2016 Elsevier Inc. All rights reserved.
  • Sawa Onouchi, Osamu Ichii, Teppei Nakamura, Yaser Hosny Ali Elewa, Yasuhiro Kon
    CELL AND TISSUE RESEARCH 365 (2) 367 - 379 0302-766X 2016/08 [Refereed][Not invited]
    Although gut flexures characterize gut morphology, the mechanisms underlying flexure formation remain obscure. Previously, we analyzed the mouse duodenojejunal flexure (DJF) as a model for its formation and reported asymmetric morphologies between the inner and outer bending sides of the fetal mouse DJF, implying their contribution to DJF formation. We now present the extracellular matrix (ECM) as an important factor for gut morphogenesis. We investigate ECM distribution during mouse DJF formation by histological techniques. In the intercellular space of the gut wall, high Alcian-Blue positivity for proteoglycans shifted from the outer to the inner side of the gut wall during DJF formation. Immunopositivity for fibronectin, collagen I, or pan-tenascin was higher at the inner than at the outer side. Collagen IV and laminins localized to the epithelial basement membrane. Beneath the mesothelium at the pre-formation stage, collagen IV and laminin immunopositivity showed inverse results, corresponding to the different cellular characteristics at this site. At the post-formation stage, however, laminin positivity beneath the mesothelium was the reverse of that observed during the pre-formation stage. High immunopositivity for collagen IV and laminins at the inner gut wall mesenchyme of the post-formation DJF implied a different blood vessel distribution. We conclude that ECM distribution changes spatiotemporally during mouse DJF formation, indicating ECM association with the establishment of asymmetric morphologies during this process.
  • Daichi Shiozuru, Osamu Ichii, Junpei Kimura, Teppei Nakamura, Yaser Hosny Ali Elewa, Saori Otsuka-Kanazawa, Yasuhiro Kon
    HISTOLOGY AND HISTOPATHOLOGY 31 (2) 189 - 204 0213-3911 2016/02 [Refereed][Not invited]
    Clarification of the renal repair process is crucial for developing novel therapeutic strategies for kidney injury. MRL/MpJ mice have a unique repair process characterized by low scar formation. The pathological features of experimentally injured MRL/MpJ and C57BL/6 mouse kidneys were compared to examine the renal repair process. The dilation and atrophy of renal tubules were observed in folic acid (FA)-induced acute kidney injury (AKI) in both strains, and the histopathological injury scores and number of interleukin (IL)-1F6-positive damaged distal tubules and kidney injury molecule 1 (KIM-1)-positive damaged proximal tubules drastically increased 1 day after AKI induction. However, KIM-1-positive tubules and the elevation of serum renal function markers were significantly fewer and lower, respectively, in MRL/MpJ mice at days 2 and 7 after AKI. After traumatic kidney injury (TKI) via needle puncture, severe tubular necrotic lesions in the punctured area and fibrosis progressed in both strains. Indices for fibrosis such as aniline blue-positive area, number of alpha smooth muscle actin-positive myofibroblasts, and messenger RNA expression levels of Tgfb1 and Mmp2 indicated lower fibrotic activity in MRL/MpJ kidneys. Characteristically, only MRL/MpJ kidneys manifested remarkable calcification around the punctured area beginning 7 days after TKI. The pathological features of injured MRL/MpJ and C57BL/6 kidneys differed, especially those of kidneys with mild proximal tubular injuries after FA-induced AKI. Lower fibrotic activity and increased calcification after TKI were observed in MRL/MpJ kidneys. These findings clarified the unique pathological characteristics of MRL/MpJ mouse kidneys and contribute to understanding of the renal repair process after kidney injury.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Yasuhiro Kon
    IMMUNOLOGY 147 (1) 30 - 40 0019-2805 2016/01 [Refereed][Not invited]
    We previously discovered mediastinal fat-associated lymphoid clusters (MFALCs) as novel lymphoid clusters associated with mediastinal fat tissue in healthy mice. However, no data about their morphology in immune-associated disease conditions, and their relationship with lung infiltration, is available to date. In the present study, we compared the morphological features of MFALCs in 4-month-old male murine autoimmune disease models (MRL/MpJ-lpr mice and BXSB/MpJ-Yaa mice) with those of the corresponding control strains (MRL/MpJ and BXSB/MpJ, respectively). In addition, we analysed their correlation with lung infiltration. Furthermore, immunohistochemistry for CD3, B220, Iba1, Gr1 and BrdU was performed to detect T cells and B cells, macrophages, granulocytes and proliferating cells, respectively. The spleen weight to body weight ratios and anti-double-stranded DNA autoantibody titres were found to be significantly higher in the autoimmune models than in the control strains. Furthermore, the autoimmune model presented prominent MFALCs, with a significantly greater ratio of lymphoid cluster area to total mediastinal fat tissue area, and more apparent diffused cellular infiltration into the lung lobes than the other studied strains. Higher numbers of T and B cells, macrophages and proliferating cells, but fewer granulocytes, were observed in the autoimmune models than in the control strains. Interestingly, a significant positive Pearson's correlation between the size of the MFALCs and the density of CD3-, B220- and Iba1-positive cells in the lung was observed. Therefore, our data suggest a potentially important role for MFALCs in the progression of lung disease. However, further investigation is required to clarify the pathological role of MFALCs in lung disease, especially in inflammatory disorders.
  • Chihara M, Nakamura T, Otsuka-Kanazawa S, Ichii O, Elewa YH, Kon Y
    Andrology 3 (5) 991 - 999 2047-2919 2015/09 [Refereed][Not invited]
  • Otsuka-Kanazawa S, Ichii O, Kon Y
    Mechanisms of development 137 23 - 32 0925-4773 2015/08 [Refereed][Not invited]
  • Onouchi S, Ichii O, Otsuka-Kanazawa S, Kon Y
    Cell and tissue research 360 (2) 273 - 285 0302-766X 2015/05 [Refereed][Not invited]
  • Yamashita Y, Nakamura T, Otsuka-Kanazawa S, Ichii O, Kon Y
    The Japanese journal of veterinary research 63 (1) 25 - 36 0047-1917 2015/02 [Refereed][Not invited]
  • Otani Y, Ichii O, Otsuka-Kanazawa S, Chihara M, Nakamura T, Kon Y
    Autoimmunity 48 (6) 402 - 411 0891-6934 2015 [Refereed][Not invited]
  • Kamikawa A, Sugimoto S, Ichii O, Kondoh D
    PloS one 10 (10) e0141131  2015 [Refereed][Not invited]
  • Junpei Kimura, Osamu Ichii, Kosuke Miyazono, Teppei Nakamura, Taro Horino, Saori Otsuka-Kanazawa, Yasuhiro Kon
    SCIENTIFIC REPORTS 4 7290  2045-2322 2014/12 [Refereed][Not invited]
    Members of the Toll-like receptor (TLR) family serve as pathogen sensors and participate in local autoimmune responses. This study found a correlation between glomerular injury and TLR expression by analysing BXSB/MpJ-Yaa (BXSB-Yaa) lupus model mice. In isolated glomeruli, the mRNA expression of several TLRs was higher in BXSB-Yaa mice than in healthy control BXSB mice. In particular, the expression of Tlr8 and its downstream cytokines was markedly increased. In mouse kidneys, TLR8 protein and mRNA localized to podocytes, and TLR8 protein expression in the glomerulus was higher in BXSB-Yaa mice than in BXSB mice. In BXSB-Yaa mice, the glomerular levels of Tlr8 mRNA negatively correlated with the glomerular levels of podocyte functional markers (Nphs1, Nphs2, and Synpo) and positively correlated with urinary albumin levels. Furthermore, the glomerular and serum levels of miR-21, a putative microRNA ligand of TLR8, were higher in BXSB-Yaa mice than in BXSB mice. The urinary levels of Tlr8 mRNA were also higher in BXSB-Yaa mice than in BXSB mice. In conclusion, the overexpression of TLR8 correlates with the progression of podocyte injury in glomerulonephritis. Thus, altered levels of urinary Tlr8 mRNA might reflect podocyte injury.
  • Y. Okada, T. Nakamura, O. Ichii, S. Otsuka, Y. Kon
    LUPUS 23 (11) 1112 - 1123 0961-2033 2014/10 [Refereed][Not invited]
    We examined the role of Mag, an autoimmune susceptibility locus encoded by the telomeric region of MRL/MpJ mouse chromosome 1, in the pathogenesis of autoimmune exocrinopathy. At nine to 12 months of age, strain-specific differences were observed in the pancreas of the animals. B- and T-cell-containing periductal/perivascular cell infiltrations in the pancreases of MRL/MpJ and B6.MRLc1 congenic C57BL/6-background Mag-carrying strains were more severe than were those of C57BL/6. Pancreatic periductal/perivascular cell infiltration was observed frequently in A/J, AKR/N, B6.MRLc1, C57BL/6, and MRL/MpJ, moderately in DBA/1 and DBA/2, and rarely in BALB/c and C3H/He strains. Females tended to have greater pancreatic periductal/perivascular cell infiltration than males. C57BL/6 mice possessed defined borders between cell infiltrations and acini, but borders were indistinct in MRL/MpJ and B6.MRLc1 mice. We attributed this to the invasion of inflammatory cells between each acinus and the disruption of acinar cells around cell infiltrations in the latter strains. No strain-specific differences were observed in the appearance of fibrotic lesions and high endothelial venules in the cell infiltrates. The levels of serum anti-dsDNA antibodies and amylase, and mRNA expression of tumor necrosis factor- and Fc gamma receptor III (encoded on Mag) in the pancreases, were elevated in MRL/MpJ- and B6.MRLc1-strain mice relative to C57BL/6. These results emphasized the crucial roles of Mag in the molecular and genetic pathogenesis of autoimmune-mediated pancreatitis.
  • Osamu Ichii, Saori Otsuka-Kanazawa, Taro Horino, Junpei Kimura, Teppei Nakamura, Manabu Matsumoto, Makoto Toi, Yasuhiro Kon
    PLOS ONE 9 (10) e110383  1932-6203 2014/10 [Refereed][Not invited]
    MicroRNAs contribute to the pathogenesis of certain diseases and may serve as biomarkers. We analyzed glomerular microRNA expression in B6. MRLc1, which serve as a mouse model of autoimmune glomerulonephritis. We found that miR-26a was the most abundantly expressed microRNA in the glomerulus of normal C57BL/6 and that its glomerular expression in B6. MRLc1 was significantly lower than that in C57BL/6. In mouse kidneys, podocytes mainly expressed miR-26a, and glomerular miR-26a expression in B6. MRLc1 mice correlated negatively with the urinary albumin levels and podocyte-specific gene expression. Puromycin-induced injury of immortalized mouse podocytes decreased miR-26a expression, perturbed the actin cytoskeleton, and increased the release of exosomes containing miR-26a. Although miR-26a expression increased with differentiation of immortalized mouse podocytes, silencing miR-26a decreased the expression of genes associated with the podocyte differentiation and formation of the cytoskeleton. In particular, the levels of vimentin and actin significantly decreased. In patients with lupus nephritis and IgA nephropathy, glomerular miR-26a levels were significantly lower than those of healthy controls. In B6. MRLc1 and patients with lupus nephritis, miR-26a levels in urinary exosomes were significantly higher compared with those for the respective healthy control. These data indicate that miR-26a regulates podocyte differentiation and cytoskeletal integrity, and its altered levels in glomerulus and urine may serve as a marker of injured podocytes in autoimmune glomerulonephritis.
  • Yaser Hosny Ali Elewa, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon
    CELL AND TISSUE RESEARCH 357 (3) 731 - 741 0302-766X 2014/09 [Refereed][Not invited]
    The association between adipose tissue and immunity has been established and fat-associated lymphoid clusters (FALCs) are considered as a source of immune cells. We discovered lymphoid clusters (LCs) in mouse mediastinal fat tissues (MFTs). In Th1-biased C57BL/6N (B6), Th2-biased DBA/2Cr (DBA) and autoimmune-prone MRL/MpJ (MRL) mice strains, LCs without a fibrous capsule and germinal center were observed in white-colored MFTs extending from the diaphragm to the heart. The number and size of the LCs were larger in 12-month-old mice than in 3-month-old mice in all of the examined strains. Moreover, B6 had an especially large number of LCs compared with DBA and MRL. The immune cells in the LCs consisted of mainly T-cells and some B-cells. The majority of T-cells were CD4+ helper T (Th) cells, rather than CD8+ cytotoxic T-cells and no obvious immune cell population difference was present among the strains. Furthermore, high endothelial venules and lymphatic vessels in the LCs were better developed in B6 mice than in the other strains. Interestingly, some CD133+ hematopoietic progenitor cells and some c-Kit+/CD127+ natural helper cells were detected in the LCs. BrdU+ proliferating cells were more abundant in the LCs of B6 mice than in the LCs of the other strains and the number of BrdU+ cells increased with age. This is the first report of LCs in mouse MFTs. We suggest that the mouse genetic background affects LC size and number. We term the LCs "mediastinal fat-associated lymphoid clusters". These clusters can be considered as niches for Th cell production.
  • Masataka Chihara, Teppei Nakamura, Naoki Sakakibara, Saori Otsuka, Osamu Ichii, Yasuhiro Kon
    AMERICAN JOURNAL OF PATHOLOGY 184 (9) 2480 - 2492 0002-9440 2014/09 [Refereed][Not invited]
    Spermatocytes of MRL/MpJ mice are more heat resistant than those of C57BL/6 mice in experimental cryptorchidism. This phenotype depends in part on the locus at the 81-cM region of MRL/MpJ-type chromosome 1 (Chr 1). To evaluate the function of this locus, we examined pathological changes in mouse testes resulting from transient scrotal heat stress. Immediately after scrotal heat stress, meiosis progression and blood-testis barrier integrity were preserved in MRL/MpJ but not in C57BL/6 mice, nor in a C57BL/6-based congenic strain carrying the MRL/MpJ-derived Chr 1 locus (B6.MRLc1). Testicular damage was severe in the weeks after scrotal heat stress in all three strains; however, testicular calcification was observed only in C57BL/6 and MRL/MpJ mice (initially as nanocrystals in mitochondria of degenerating germ cells). In testes, expression of gremlin 2, a bone morphogenetic protein antagonist encoded on Chr 1, was markedly higher in B6.MRLc1 than in C57BL/6 or MRL/Mp3 mice. Furthermore, gremlin-2 and bone morphogenetic protein 2 mRNA levels in heated testes correlated negatively and positively, respectively, with calcification. Thus, although the MRL/MpJ-derived Locus on Chr 1 may play a pivotal role in recovery from heat-induced testicular damage, especially via inhibition of calcification, MRL/MpJ mice have a precipitating factor for testicular calcification and heat shock-resistant factors that reside outside the 81-cM region of Chr 1.
  • Osamu Ichii, Saori Otsuka-Kanazawa, Teppei Nakamura, Masaaki Ueno, Yasuhiro Kon, Weiping Chen, Avi Z. Rosenberg, Jeffrey B. Kopp
    PLOS ONE 9 (9) e108448  1932-6203 2014/09 [Refereed][Not invited]
    Indoxyl sulfate is a uremic toxin and a ligand of the aryl-hydrocarbon receptor (AhR), a transcriptional regulator. Elevated serum indoxyl sulfate levels may contribute to progressive kidney disease and associated vascular disease. We asked whether indoxyl sulfate injures podocytes in vivo and in vitro. Mice exposed to indoxyl sulfate for 8 w exhibited prominent tubulointerstitial lesions with vascular damage. Indoxyl sulfate-exposed mice with microalbuminuria showed ischemic changes, while more severely affected mice showed increased mesangial matrix, segmental solidification, and mesangiolysis. In normal mouse kidneys, AhR was predominantly localized to the podocyte nuclei. In mice exposed to indoxyl sulfate for 2 h, isolated glomeruli manifested increased Cyp1a1 expression, indicating AhR activation. After 8 w of indoxyl sulfate, podocytes showed foot process effacement, cytoplasmic vacuoles, and a focal granular and wrinkled pattern of podocin and synaptopodin expression. Furthermore, vimentin and AhR expression in the glomerulus was increased in the indoxyl sulfate-exposed glomeruli compared to controls. Glomerular expression of characteristic podocyte mRNAs was decreased, including Actn4, Cd2ap, Myh9, Nphs1, Nphs2, Podxl, Synpo, and Wt1. In vitro, immortalized-mouse podocytes exhibited AhR nuclear translocation beginning 30 min after 1 mM indoxyl sulfate exposure, and there was increased phospho-Rac1/Cdc42 at 2 h. After exposure to indoxyl sulfate for 24 h, mouse podocytes exhibited a pro-inflammatory phenotype, perturbed actin cytoskeleton, decreased expression of podocyte-specific genes, and decreased cell viability. In immortalized human podocytes, indoxyl sulfate treatment caused cell injury, decreased mRNA expression of podocyte-specific proteins, as well as integrins, collagens, cytoskeletal proteins, and bone morphogenetic proteins, and increased cytokine and chemokine expression. We propose that basal levels of AhR activity regulate podocyte function under normal conditions, and that increased activation of podocyte AhR by indoxyl sulfate contributes to progressive glomerular injury.
  • Y. H. A. Elewa, O. Ichii, S. Otsuka, Y. Hashimoto, Y. Kon
    ANATOMIA HISTOLOGIA EMBRYOLOGIA 43 (4) 265 - 272 0340-2096 2014/08 [Refereed][Not invited]
    Previously, the structure of the adult goat parotid salivary glands (PGs) was studied. However, little information was elucidated of the juvenile ones. This study aimed to clarify the correlations between the structure of goats' PGs and the nature of food intake among milk-suckling kids (MSKs) and diet-fed goats (DFGs). The secretory endpieces of the goats' PGs are of the pure serous type. The serous cells in MSKs showed apical accumulation of numerous secretory granules (SGs) of smaller size and of more intense positive periodic acid-Schiff reaction. Ultrastructurally, most of the SGs in the DFGs contained peripherally located inclusions that showed dense reaction products for acid phosphatase. In MSKs, the PGs showed less-developed basal infoldings, sparseness of the inter-cellular inter-digitations, fewer inter-cellular canaliculi and microvilli and also less-developed myoepithelial cells with fewer and shorter cytoplasmic processes. In conclusion, the less-developed membrane specializations and myoepithelial cells, as well as the accumulated SGs in the PGs of MSKs, suggest that it secretes less saliva with a little secretory activity than that of DFGs, which may be correlated with the reduced masticatory activity.
  • Teppei Nakamura, Yuko Sakata, Saori Otsuka-Kanazawa, Osamu Ichii, Masataka Chihara, Ken-ichi Nagasaki, Yuka Namiki, Yasuhiro Kon
    PLOS ONE 9 (6) e100617  1932-6203 2014/06 [Refereed][Not invited]
    In MRL/MpJ mice, ovarian mast cells (OMCs) are more abundant than in other mouse strains, and tend to distribute beneath the ovarian surface epithelium at birth. This study investigated the factors regulating the appearance of neonatal OMCs in progeny of the cross between MRL/MpJ and C57BL/6N strains. F1 neonates had less than half the number of OMCs than MRL/MpJ. Interestingly, MRLB6F1 had more neonatal OMCs than B6MRLF1, although they were distributed over comparable areas. Furthermore, in MRL/MpJ fetuses for which parturition was delayed until embryonic day 21.5, the number of OMCs was significantly higher than in age-matched controls at postnatal day 2. These results suggest that the number of OMCs was influenced by the environmental factors during pregnancy. Quantitative trait locus analysis using N2 backcross progeny revealed two significant loci on chromosome 8: D8Mit343-D8Mit312 for the number of OMCs and D8Mit86-D8Mit89 for their distribution, designated as mast cell in the ovary of MRL/MpJ 1 (mcom1) and mcom2, respectively. Among MC migration-associated genes, ovarian expression of chemokine (C-C motif) ligand 17 at mcom1 locus was significantly higher in MRL/MpJ than in C57BL/6N, and positively correlated with the expression of OMC marker genes. These results indicate that the appearance of neonatal OMCs in MRL/MpJ is controlled by environmental factors and filial genetic factors, and that the abundance and distribution of OMCs are regulated by independent filial genetic elements.
  • Minato Hirano, Kentaro Yoshii, Mizuki Sakai, Rie Hasebe, Osamu Ichii, Hiroaki Kariwa
    JOURNAL OF GENERAL VIROLOGY 95 (Pt 4) 849 - 861 0022-1317 2014/04 [Refereed][Not invited]
    Neurological diseases caused by encephalitic flaviviruses are severe and associated with high levels of mortality. However, detailed mechanisms of viral replication in the brain and features of viral pathogenesis remain poorly understood. We carried out a comparative analysis of replication of neurotropic flaviviruses: West Nile virus, Japanese encephalitis virus and tick-borne encephalitis virus (TBEV), in primary cultures of mouse brain neurons. All the flaviviruses multiplied well in primary neuronal cultures from the hippocampus, cerebral cortex and cerebellum. The distribution of viral-specific antigen in the neurons varied: TBEV infection induced accumulation of viral antigen in the neuronal dendrites to a greater extent than infection with other viruses. Viral structural proteins, non-structural proteins and dsRNA were detected in regions in which viral antigens accumulated in dendrites after TBEV replication. Replication of a TBEV replicon after infection with virus-like particles of TBEV also induced antigen accumulation, indicating that accumulated viral antigen was the result of viral RNA replication. Furthermore, electron microscopy confirmed that TBEV replication induced characteristic ultrastructural membrane alterations in the neurites: newly formed laminal membrane structures containing virion-like structures. This is the first report describing viral replication in and ultrastructural alterations of neuronal dendrites, which may cause neuronal dysfunction. These findings encourage further, work aimed at understanding the molecular mechanisms of viral replication in the brain and the pathogenicity of neurotropic flaviviruses.
  • J. Kimura, O. Ichii, T. Nakamura, T. Horino, S. Otsuka, Y. Kon
    GENES AND IMMUNITY 15 (3) 182 - 189 1466-4879 2014/04 [Refereed][Not invited]
    The autoimmune-prone BXSB/MpJ-Yaa mouse is a model of membranous proliferative glomerulonephritis (MPGN). Severe MPGN has been reported only in male BXSB/MpJ-Yaa mice because of the Y-linked autoimmune accelerator (Yaa) locus. However, we show that female BXSB/MpJ mice develop age-related MPGN without Yaa. Female BXSB/MpJ mice clearly developed MPGN characterized by increased mesangial cells, thickening of the glomerular basement membrane (GBM), double contouring and spike formation of GBM with T-cell infiltrations and podocyte injuries corresponding with increased autoantibody production and albuminuria. Analysis of the renal levels of the Fc gamma receptor (Fcgr) and interferon-activated gene 200 (Ifi200) family genes, which are MPGN candidate genes localized to the telomeric region of chromosome 1 (Chr.1), showed that Fcgr2b levels decreased, whereas Fcgr3 and Ifi202b levels increased in female BXSB/MpJ mice compared with healthy C57BL/6 mice. Furthermore, in isolated glomeruli, microarray analysis revealed that Fcgr3, Fcgr4 and Ifi202b expression was higher in male BXSB/MpJ-Yaa mice than in male BXSB/MpJ mice. These findings indicate that the BXSB/MpJ-type genome causes age-related MPGN with significant contribution from the telomeric region of Chr.1, and Yaa? enhances the expression of genes localizing to this locus, thereby leading to severe MPGN in male mice.
  • Osamu Ichii, Saori Otsuka, Hiroshi Ohta, Akira Yabuki, Taro Horino, Yasuhiro Kon
    RESEARCH IN VETERINARY SCIENCE 96 (2) 299 - 303 0034-5288 2014/04 [Refereed][Not invited]
    MicroRNAs (miRNAs) play a role in the pathogenesis of certain diseases and may serve as biomarkers. Here, we present the first analysis of miRNA expression in the kidneys of healthy cats and dogs. Kidneys were divided into renal cortex (CO) and medulla (MD), and RNA sequence analysis was performed using the mouse genome as a reference. A total of 277, 276, 295, and 297 miRNAs were detected in cat CO, cat MD, dog CO, and dog MD, respectively. By comparing the expression ratio of CO to MD, we identified highly expressed miRNAs in each tissue as follows: 41 miRNAs including miR-192-5p in cat CO; 45 miRNAs including miR-323-3p in dog CO; 78 miRNAs including miR-20a-5p in cat MD; and 11 miRNAs including miR-132-5p in dog MD. Further, the target miRNAs of these miRNAs were identified. These data provide veterinary medicine critical information regarding renal miRNA expression. (C) 2014 Elsevier Ltd. All rights reserved.
  • Chihara M, Otsuka S, Ichii O, Kon Y
    The Journal of reproduction and development 59 (6) 525 - 535 0916-8818 2013/12 [Refereed][Not invited]
  • Keigo Kosenda, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon
    CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 41 (8) 788 - 797 1442-6404 2013/11 [Refereed][Not invited]
    BackgroundDacryoadenitis is characteristic of an autoimmune exocrinopathy, e.g. Sjogren syndrome. We pathologically examined the lacrimal glands of autoimmune-prone BXSB/MpJ-Yaa mice for the appearance of pathological signs of dacryoadenitis progression in autoimmune dacryoadenitis models, particularly focusing on messenger RNAs in the lacrimal fluid. MethodsThe lacrimal glands of the BXSB/MpJ-Yaa and C57BL/6 mice were histopathologically analyzed in parallel with the evaluation of lacrimation and messenger RNA expression of water channels (Aqp3, Aqp4 and Aqp5). In addition, autoimmune model mice (MRL/MpJ-lpr/lpr and NZB/NZWF1) were used for evaluating cell infiltration and detecting inflammatory cell marker messenger RNAs (Cd68, Ptprc and Cd3e) in the lacrimal fluids by polymerase chain reaction-based methods. ResultsB-cell predominant lymphocytic infiltrations and the destruction of acini were observed in the lacrimal glands of BXSB/MpJ-Yaa mice. There was no significant difference in the quantity of lacrimal fluid between the BXSB/MpJ-Yaa and C57BL/6 mice. In the BXSB/MpJ-Yaa mice, Aqp3 expression increased significantly with the cell infiltration score, whereas expression of Aqp4 and Aqp5 tended to decrease. Aqp3 expression increased significantly with the cell infiltration score in BXSB/MpJ-Yaa mice. Among inflammatory cell markers, Cd68 was more frequently detected in the lacrimal fluid of the BXSB/MpJ-Yaa, MRL/MpJ-lpr/lpr and NZB/NZWF1 mice than in that of the C57BL/6 mice. ConclusionBXSB/MpJ-Yaa mice clearly developed autoimmune dacryoadenitis. The altered expression of water channels in lacrimal glands might be associated with the preservation of lacrimal fluid excretion in BXSB/MpJ-Yaa mice. The detection of inflammatory cell markers in lacrimal fluid could be used as a diagnostic marker for autoimmune dacryoadenitis.
  • Sawa Onouchi, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon
    JOURNAL OF ANATOMY 223 (4) 385 - 398 0021-8782 2013/10 [Refereed][Not invited]
    Abstract The mammalian gut undergoes morphological changes during development. We studied the developing mouse duodenojejunal flexure (DJF) to elucidate the mechanism of formation. During embryonic days 10.75-13.75, DJF formation was morphologically classified into three stages: the expansion stage, flexure formation stage, and flexure elongation stage. From the expansion to the flexure formation stages, the DJF wall showed asymmetric morphology and proliferation along the left-right intestinal axis. From the flexure formation to the flexure elongation stage, the DJF started to bend dorsally with counterclockwise rotation along the antero-caudal intestinal axis, indicating that the original right side of the duodenum was rotated towards the dorsal body wall during development of the DJF. The direction of attachment of the dorsal mesentery to the DJF did not correspond to the bending direction of the DJF during flexure formation, and this finding indicated that the dorsal mesentery contributed very little to DJF formation. During DJF formation, Aldh1a2 and hedgehog mRNAs were detected at the DJF, and their expression levels differed along the bending axis. In conclusion, DJF formation might be triggered by asymmetric morphology and proliferation along the left-right intestinal axis under the control of retinoic acid and hedgehog signaling.
  • Teppei Nakamura, Saori Otsuka, Osamu Ichii, Yuko Sakata, Ken-Ichi Nagasaki, Yoshiharu Hashimoto, Yasuhiro Kon
    PLOS ONE 8 (10) e77246  1932-6203 2013/10 [Refereed][Not invited]
    In the neonatal mouse ovary, clusters of oocytes called nests break into smaller cysts and subsequently form individual follicles. During this period, we found numerous mast cells in the ovary of MRL/MpJ mice and investigated their appearance and morphology with follicular development. The ovarian mast cells, which were already present at postnatal day 0, tended to localize adjacent to the surface epithelium. Among 11 different mouse strains, MRL/MpJ mice possessed the greatest number of ovarian mast cells. Ovarian mast cells were also found in DBA/1, BALB/c, NZW, and DBA/2 mice but rarely in C57BL/6, NZB, AKR, C3H/He, CBA, and ICR mice. The ovarian mast cells expressed connective tissue mast cell markers, although mast cells around the surface epithelium also expressed a mucosal mast cell marker in MRL/MpJ mice. Some ovarian mast cells migrated into the oocyte nests and directly contacted the compressed and degenerated oocytes. In MRL/MpJ mice, the number of oocytes in the nest was significantly lower than in the other strains, and the number of oocytes showed a positive correlation with the number of ovarian mast cells. The gene expression of a mast cell marker also correlated with the expression of an oocyte nest marker, suggesting a link between the appearance of ovarian ? 4mast cells and early follicular development. Furthermore, the expression of follicle developmental markers was significantly higher in MRL/MpJ mice than in C57BL/6 mice. These results indicate that the appearance of ovarian mast cells is a unique phenotype of neonatal MRL/MpJ mice, and that ovarian mast cells participate in early follicular development, especially nest breakdown.
  • Masataka Chihara, Ryoyo Ikebuchi, Saori Otsuka, Osamu Ichii, Yoshiharu Hashimoto, Atsushi Suzuki, Yumiko Saga, Yasuhiro Kon
    BIOLOGY OF REPRODUCTION 89 (1) 3  0006-3363 2013/07 [Refereed][Not invited]
    Claudin 3 is a protein component of the tight junction strands. Tight junctions between adjacent Sertoli cells form the blood-testis barrier (BTB). During spermatogenesis, seminiferous stage-specific expression of claudin 3 is believed to regulate the migration of preleptotene/leptotene spermatocytes across the BTB. Here, we determined the cell types expressing claudin 3 in adult mouse testis and investigated spermatogenesis after testis-specific in vivo knockdown of claudin 3. The results of in situ hybridization revealed that claudin 3 mRNA was predominantly expressed in germ cells near the basal lamina of seminiferous tubules at stages VI-IX. Furthermore, claudin 3 protein was localized not only to the BTB but also to the cell membrane of STRA8-expressing preleptotene/leptotene spermatocytes in the testis of adult ICR. Cg-Tg(Stra8-EGFP)1Ysa/YsaRbrc mice. Although claudin 3 knockdown did not affect BTB integrity, it did cause a partial delay in spermatocyte migration across the BTB. Moreover, claudin 3 knockdown resulted in a prolonged preleptotene phase during spermatogenesis. These data indicate that the seminiferous stage-specific expression and localization of claudin 3 during spermatogenesis regulate the progression of meiosis by promoting germ cell migration across the BTB.
  • Yuki Naganuma, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon
    JOURNAL OF VETERINARY MEDICAL SCIENCE 75 (3) 283 - 290 0916-7250 2013/03 [Refereed][Not invited]
    Caspase activation is associated with skeletal muscle differentiation in mouse embryos. We examined the relationship between cardiac myogenesis and cell death using mice hearts at embryonic days (E) 11.5-15.5 and fetal rat heart H9C2 cells. The number of TdT-mediated dUTP nick erid labeling (TUNEL)-positive cells increased with fetal age and was much higher than that of single-stranded DNA (ssDNA)- and active caspase-3 (aCasp3)-positive cells. TUNEL and aCasp3 double staining resulted in 3 types of positive cells: TUNEL+/aCasp3(+), TUNEL+/aCasp3(-) and TUNEL-/aCasp3(+). TUNEL+/aCasp3(-) cells were the most common but lacked morphological features of apoptosis, such as nuclear condensation or fragmentation. The expression of anti-apoptotic factors increased during E11.5-15.5. Furthermore, TUNEL-positive H9C2 cells without nuclear condensation or fragmentation were observed only in myotubes later in the culture period. In this study, the dynamics of TUNEL-positive cardiomyocyte was inconsistent with the activation of apoptosis cascade, and their morphological feature was clearly different from representative apoptosis. From these findings, we concluded that the increased number of TUNEL-positive cardiomyocyte, having the DNA strand breaks, would be associated with the progression of cardiac myogenesis.
  • Kimura J, Ichii O, Otsuka S, Sasaki H, Hashimoto Y, Kon Y
    American journal of nephrology 38 (1) 27 - 38 0250-8095 2013 [Refereed][Not invited]
  • Saori Otsuka, Osamu Ichii, Yuka Namiki, Nobuya Sasaki, Yoshiharu Hashimoto, Yasuhiro Kon
    MAMMALIAN GENOME 23 (11-12) 741 - 748 0938-8990 2012/12 [Refereed][Not invited]
    Mammals produce sperm or oocytes depending on their sex; however, newborn MRL/MpJ (MRL) male mice produce oocytes within their testes. We previously reported that one of the genes responsible for this phenotype is present on the MRL-type Y chromosome (Y-MRL), and that multiple genes, probably autosomal, are also required for the development of this phenotype. In this study we focused on the autosomal genes and examined their relationship with this phenotype by analyzing the progeny from crosses between MRL mice and other strains. We first observed the male F1 progeny from the crosses between female A/J, C57BL/6 (B6), BALB/c, C3H/He, or DBA/2 mice and male MRL mice, and two consomic strains, male B6-Y-MRL and MRL-Y-B6. Testicular oocytes that were morphologically similar to those of MRL mice were detected in all mouse strains except BALBMRLF1; however, the incidence of testicular oocytes was significantly lower than that in MRL mice. The appearance of testicular oocytes in MRL-Y-B6 mice indicates that this phenotype is strongly affected by genomic factors present on autosomes, and that there is at least one other causative gene on the MRL-type autosomes (MRL testicular oocyte production, mtop) other than that on Y-MRL. Furthermore, a quantitative trait locus (QTL) analysis using N2 backcross progeny from crosses between female MRLB6F1 and male MRL mice revealed the presence of susceptibility loci for the appearance of testicular oocytes at 8-17 cM on Chr 15. These findings demonstrate that the appearance of testicular oocytes is regulated by the genetic factors on Chr 15 and on Y-MRL.
  • Ayumi Matsuyama-Kato, Shiro Murata, Masayoshi Isezaki, Rika Kano, Sara Takasaki, Osamu Ichii, Satoru Konnai, Kazuhiko Ohashi
    VIROLOGY JOURNAL 9 94  1743-422X 2012/05 [Refereed][Not invited]
    Background: An immunoinhibitory receptor, programmed death-1 (PD-1), and its ligand, programmed death-ligand 1 (PD-L1), are involved in immune evasion mechanisms for several pathogens causing chronic infections and for neoplastic diseases. However, little has been reported for the functions of these molecules in chickens. Thus, in this study, their expressions and roles were analyzed in chickens infected with Marek's disease virus (MDV), which induces immunosuppression in infected chickens. Results: A chicken T cell line, Lee1, which constitutively produces IFN-gamma was co-cultured with DF-1 cells, which is a spontaneously immortalized chicken fibroblast cell line, transiently expressing PD-L1, and the IFN-gamma expression level was analyzed in the cell line by real-time RT-PCR. The IFN-gamma expression was significantly decreased in Lee1 cells co-cultured with DF-1 cells expressing PD-L1. The expression level of PD-1 was increased in chickens at the early cytolytic phase of the MDV infection, while the PD-L1 expression level was increased at the latent phase. In addition, the expression levels of PD-1 and PD-L1 were increased at tumor lesions found in MDV-challenged chickens. The expressions levels of PD-1 and PD-L1 were also increased in the spleens and tumors derived from MDV-infected chickens in the field. Conclusions: We demonstrated that the chicken PD-1/PD-L1 pathway has immunoinhibitory functions, and PD-1 may be involved in MD pathogenesis at the early cytolytic phase of the MDV infection, whereas PD-L1 could contribute to the establishment and maintenance of MDV latency. We also observed the increased expressions of PD-1 and PD-L1 in tumors from MDV-infected chickens, suggesting that tumor cells transformed by MDV highly express PD-1 and PD-L1 and thereby could evade from immune responses of the host.
  • Osamu Ichii, Saori Otsuka, Nobuya Sasaki, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    KIDNEY INTERNATIONAL 81 (3) 280 - 292 0085-2538 2012/02 [Refereed][Not invited]
    MicroRNAs (miRNAs) are highly conserved small non-coding RNAs that act as post-transcriptional regulators of target mRNA. In this study, we sought to identify the microRNA underlying local inflammation in a murine model of chronic kidney disease (CKD). In microarray analysis of kidneys, the expression of miR-146a/b was elevated in B6.MRLc1 CKD mice that spontaneously develop renal inflammation with age. Primary-microRNA analysis found that elevated miR-146a/b expression in the kidneys of B6.MRLc1 mice was mainly derived from miR-146a rather than miR-146b, and this expression increased with the development of CKD. Histopathological scores for glomerular and interstitial lesions, mRNA expression of inflammatory mediators, and macrophage infiltration were significantly higher in B6.MRLc1 than C57BL/6 mice and were positively correlated with miR-146a expression. In situ hybridization and laser microdissection-RT-PCR showed that miR-146a expression in interstitial lesions containing inflammatory cells was higher than in the glomerulus. The increased expression of the inflammatory-associated genes RELA, IRAK1, IL1B, IL10, and CXCLs was noted in miR-146a/b-silenced human monocytes. The amount of miR-146a was higher in urine sediments of B6.MRLc1 than of C57BL/6 mice. Thus, miR-146a expression in the kidneys and its urinary excretion was specifically associated with the development of interstitial lesions and correlated with inflammatory cell infiltration. Kidney International (2012) 81, 280-292; doi: 10.1038/ki.2011.345; published online 5 October 2011
  • Tomohiro Nishino, Nobuya Sasaki, Ken-ichi Nagasaki, Osamu Ichii, Yasuhiro Kon, Takashi Agui
    BIOMEDICAL RESEARCH-TOKYO 33 (1) 53 - 56 0388-6107 2012/02 [Refereed][Not invited]
    The ICGN mouse strain is a glomerulosclerosis (GS) model that shows significant proteinuria, podocyte morphological abnormalities and increased extracellular matrix accumulation in the glomeruli, which represent the final common pathology associated with a variety of kidney diseases leading to end-stage renal failure. Previously, we demonstrated that GS in ICGN mice can be attributed to the deletion mutation of the tensin2 (Tns2) gene (Tns2(nep)). Further, the C57BL/6J (B6) mouse is resistant to GS caused by this mutation. 129/Sv is also a popular strain; however, its susceptibility to GS has not been defined. Thus, to determine whether 129/Sv is resistant or susceptible to GS, we produced a congenic strain carrying Tns2(nep)) on the 129(+Ter)/Sv (129T) background. 129T congenic mice (129T-Tns2(nep)) did not exhibit albuminuria, renal anemia, increases in BUN, or any severe pathological changes until at least 16 weeks of age. These results indicate that 1291 is resistant to GS. Although their usage in biomedical studies is already widespread, 129/Sv mice may afford a late-onset and unique strain applicable to kidney disease research.
  • Kentaro Yoshii, Manabu Igarashi, Osamu Ichii, Kana Yokozawa, Kimihito Ito, Hiroaki Kariwa, Ikuo Takashima
    JOURNAL OF GENERAL VIROLOGY 93 (Pt 1) 27 - 38 0022-1317 2012/01 [Refereed][Not invited]
    Flaviviruses are assembled to bud into the lumen of the endoplasmic reticulum (ER) and are secreted through the vesicle transport pathway, but the details of the molecular mechanism of virion assembly remain largely unknown. In this study, a highly conserved region in the prM protein was identified among flaviviruses. In the subviral particle (SP) system of tick-borne encephalitis virus (TBEV) and Japanese encephalitis virus, secretion of SPs was impaired by a mutation in the conserved region in the prM protein. Viral proteins were sparse in the Golgi complex and accumulated in the ER. Ultrastructural analysis revealed that long filamentous structures, rather than spherical SPs, were observed in the lumen of the ER as a result of the mutation. The production of infectious virions derived from infectious cDNA of TBEV was also reduced by mutations in the conserved region. Molecular modelling analysis suggested that the conserved region is important for the association of prM-envelope protein heterodimers in the formation of a spike of immature virion. These results are the first demonstration that the conserved region in the prM protein is a molecular determinant for the flavivirus assembly process.
  • Takahiro Seto, Noriyo Nagata, Keisuke Yoshikawa, Osamu Ichii, Takahiro Sanada, Ngonda Saasa, Yuka Ozaki, Yasunori Kon, Kentaro Yoshii, Ikuo Takashima, Hiroaki Kariwa
    VIRUS RESEARCH 163 (1) 284 - 290 0168-1702 2012/01 [Refereed][Not invited]
    Hantaan virus (HTNV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). The pathogenesis of HFRS has not been fully elucidated, mainly due to the lack of a suitable animal model. In laboratory mice, HTNV causes encephalitis. However, that symptom is dissimilar to human hantavirus infections. We found that HTNV strain AA57 (isolated from Apodemus agrarius in Far East Russia) caused pulmonary disease in 2-week-old ICR mice. The clinical signs of the infected mice were piloerection, trembling, hunching, labored breathing, and body-weight loss. A large volume of pleural effusion was collected from thoracic cavities of the dead mice. Overall, 45% of the mice inoculated with 3000 focus forming units (FFU) of the virus began to show clinical symptoms at 8 days post-inoculation, and 25% of the inoculated mice died within 3 days of onset of the disease. The morbidity and mortality rates of the mice inoculated with 30-30,000 FFU of HTNV strain AA57 were roughly equivalent. The highest rates of virus positivity (11/12) and the highest titers of HTNV strain AA57 were detected in the lungs of the dead mice, while lower detection rates and viral titers were found in the heart, kidneys, spleen, and brain. Interstitial pneumonia, perivascular edema, hemorrhage, inflammatory infiltration and vascular failure were observed in the lungs of the sick mice. Hantaviral antigens were detected in the lung endothelial cells of the sick mice. The symptoms and pathology of this mouse model resemble those of hantavirus pulmonary syndrome (HPS) and, to a certain extent, those of HFRS. This is the first report that, in laboratory mice, the HFRS-related hantavirus causes a HPS-like disease and shares some symptom similarities with HFRS. (C) 2011 Elsevier B.V. All rights reserved.
  • Shin-Hyo Lee, Osamu Ichii, Saori Otsuka, Elewa Yaser Hosney, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    JOURNAL OF ANATOMY 219 (6) 743 - 755 0021-8782 2011/12 [Refereed][Not invited]
    MRL/MpJ (MRL) mice, commonly used as a model for autoimmune disease, have a high frequency of ovarian cysts originating from the rete ovarii. In the present study, to clarify how the rete ovarii, which are remnants of mesonephric tubules during embryogenesis, progress to cystic formation with aging, the morphology of MRL rete ovarii was analyzed and compared with that of normal C57BL/6N (B6) mice. In B6 mice, the rete ovarii consisted of a series of tubules, including the extraovarian rete (ER), the connecting rete (CR), and the intraovarian rete (IR), based on their location. Whereas the ER of B6 mice was composed of highly convoluted tubules lined by both ciliated and non-ciliated epithelia, the tubules in the CR and IR had only non-ciliated cells. In MRL mice, dilations of the rete ovarii initiated from the IR rather than the ER or CR. Although the histological types of cells lining the lumen of the rete ovarii were the same as those in B6 mice, the ER in MRL mice showed a variety in morphology. In particular, the connections between the ER and ovary tended to disappear with increasing age and the development of ovarian cysts. Furthermore, the epithelium lining the large ovarian cysts in MRL mice had ciliated cells forming the cluster. On the basis of these findings, it is suggested that cystic changes of the rete ovarii in MRL mice are caused by the dilations of the IR with invasion of the ER and CR into the ovarian medulla. These data provide new pathological mechanisms for ovarian cyst formation.
  • Osamu Ichii, Akira Yabuki, Nobuya Sasaki, Saori Otsuka, Hiroshi Ohta, Masahiro Yamasaki, Mitsuyoshi Takiguchi, Yuka Namiki, Yoshiharu Hashimoto, Daiji Endoh, Yasuhiro Kon
    HISTOLOGY AND HISTOPATHOLOGY 26 (10) 1243 - 1255 0213-3911 2011/10 [Refereed][Not invited]
    Podocytes cover the glomerulus and their adjacent foot processes form a principal barrier called the slit diaphragm. Podocyte dysfunctions, including podocyte loss and slit diaphragm disruptions, induce chronic kidney diseases (CKD). In this study, we analyzed the correlations between podocyte injuries and renal dysfunctions in domestic carnivores. Dogs and cats were divided into normal and CKD groups according to renal histopathology and plasma creatinine values. Immunostaining results showed that linear reactions of slit diaphragm molecules, e. g., nephrin, podocin, and ACTN4, were parallel to glomerular capillaries in all animals. However, in dogs, reactions of nephrin and ACTN4 were changed to a granular pattern in the CKD group, and their intensities significantly decreased with the number of podocytes in the glomerulus. Moreover, the expression of nephrin and ACTN4 negatively correlated with creatinine. Real-time PCR analysis showed that nephrin mRNA expression in the kidneys of CKD dogs was significantly lower than that in normal animals, and negatively correlated with creatinine. Although no significant correlation between renal dysfunction and podocyte injury was detected in cats, histoplanimetric scores of tubulointerstitial lesions in CKD cats were higher than those in both normal cats and diseased dogs. Furthermore, mRNAs of WT1 and SD molecules were detected in urine from CKD animals. In conclusion, podocyte injuries such as podocytopenia and decreased expression of nephrin and ACTN4 in the glomerulus were more strongly correlated with renal dysfunction in dogs than in cats. These findings suggest that the CKD pathogenesis, especially susceptibilities to podocyte injuries, differed between dogs and cats.
  • Ayo Yila Simon, Nobuya Sasaki, Osamu Ichii, Kiichi Kajino, Yasuhiro Kon, Takashi Agui
    MICROBES AND INFECTION 13 (8-9) 783 - 797 1286-4579 2011/08 [Refereed][Not invited]
    Respiratory viral infections result in severe pulmonary injury, to which host immune response may be a significant contributor. At present, it is not entirely clear the extent to which lung injury is a necessary consequence of host defense. In this report, we use functional genomics approach to characterize the key roles of cellular immunity and immune-inflammatory response in the immunopathology of Sendai virus infection in resistant C57BL/6J and susceptible DBA/2J mice. Infected mice manifested an immune-inflammatory response characterized by the pulmonary influx of neutrophils and mononuclear cells. DBA/2J mice mounted a vigorous immune response, with significant up-regulation of cytokine/chemokine genes in two successive waves through the course of infection. Whereas, C57BL/6J mice displayed an efficient immune response with less severe pathology and clusters of immune-inflammatory responsive genes were exclusively up-regulated on day 4 in this strain. Overall, DBA/2J mice exhibited a dysregulated hyper-inflammatory cytokine/chemokine cascades that does not limit viral spread resulting in a predisposition to severe lung pathology. This response is similar to severe human respiratory paramyxovirus infections, which will serve as a model for the elucidation of hyper-immune inflammatory response that result to severe immunopathology in respiratory viral infections. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
  • Identifying a new locus that regulates the development of rete ovarian cysts in MRL/MpJ mice
    Shin-Hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yuka Namiki, Yasuhiro Kon
    JAPANESE JOURNAL OF VETERINARY RESEARCH 59 (2-3) 79 - 88 0047-1917 2011/08 [Refereed][Not invited]
    MRL/MpJ (MRL) is a mouse model for autoimmune disease and develops ovarian cysts with age. The ovarian cysts originate from the rete ovarii, which is considered to be the remnant of fetal mesonephric tubules. In a previous study, we analyzed the genetic background of ovarian cysts by using backcross progenies between MRL and C57BL/6N (B6) mice. By interval mapping, suggestive linkages were detected on several chromosomes (Chrs), and a significant linkage on Chr 14 was designated as MRL Rete Ovarian Cyst (mroc). In the present study, which evaluated 113 F2 intercross progenies, a significant linkage appeared on Chr 6 at the marker position D6Mit188 (likelihood ratio statistic = 18.5). In particular, the peak regions of Chrs 6 and 14, which contain major causative loci by backcross analysis, showed close reverse interaction. From these results, a locus on Chr 6 was identified as mroc2, the second major locus associated with ovarian cyst formation in MRL mice.
  • Tomonori Kanazawa, Osamu Ichii, Saori Otsuka, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    JOURNAL OF VETERINARY MEDICAL SCIENCE 73 (5) 601 - 607 0916-7250 2011/05 [Refereed][Not invited]
    During kidney development, the metanephric mesenchyme (MM) develops into the nephron through mesenchymal-epithelial transition (MET). We have previously reported that knock-down of the expression of hepatocyte nuclear factor 4 alpha (Huf4a) gene induces failure of cellular organization in the condensed mesenchyme (CM) of cultured embryonic kidneys. To elucidate the details of MET during nephrogenesis, embryonic mouse kidneys were analyzed by electron microscopy, immunohistochemistry, and molecular biology. The findings showed that the intercellular junction, but not the basal lamina, was present in the CM. Additionally, immediately after Hnf4a gene expression, the expression of epithelial genes (Krt8, Tjp1, and Cdh1) increased, and those of mesenchymal genes (Acta1 and Vim) decreased, in the CM compared to the MM. To clarify the relationship between MET and Hnf4 alpha, the fibroblast cell line with forced expression of Hnf4 alpha protein were analyzed. In this model, it was noted that Hnf4a induced increasing epithelial and decreasing mesenchymal gene expression. In these, up-regulation of Pvrl1, -2, and Mllt4 genes which mediate the formation of apico-basal polarity, were found. These results, and those of previous findings, indicate that Hnf4 alpha protein is associated with the initiation of MET in early nephrogenesis.
  • Daisuke Torigoe, Osamu Ichii, Ruihua Dang, Takayuki Ohnaka, Shinya Okano, Nobuya Sasaki, Yasuhiro Kon, Takashi Agui
    JOURNAL OF VETERINARY MEDICAL SCIENCE 73 (5) 707 - 710 0916-7250 2011/05 [Refereed][Not invited]
    To identify a gene responsible for the hooded phenotype in the rat, high-resolution linkage mapping for the hooded locus was performed using IS (non-hooded) and LEA (hooded) rats. The map revealed that only Kit gene existed in the critical region, suggesting that the Kit is a strong candidate gene. However, mutation was not found in the coding region of the LEA rat Kit gene. Further, the expressions of Kit mRNA were not different in fetal neural tubes and both neonatal and adult skins between IS and LEA rats. Furthermore, Kit-positive cells, possibly melanocytes, were found in the non-pigmented hair follicles of hooded phenotype rats. Several hypotheses are conceivable to account for mechanisms in the appearance of hooded phenotype.
  • Junpei Kimura, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Yuka Namiki, Yoshiharu Hashimoto, Yasuhiro Kon
    PLOS ONE 6 (1) e16472  1932-6203 2011/01 [Refereed][Not invited]
    The kidney is a nonregenerative organ composed of numerous functional nephrons and collecting ducts (CDs). Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology. Urinary cytology and renal histopathology were analyzed in BXSB/MpJ (BXSB; glomerulonephritis model) and C57BL/6 (B6; control) mice. Urinary cytology revealed that the number of urinary cells in BXSB mice changed according to the histometric score of glomerulonephritis and urinary albumin; however, no correlation was detected for the levels of blood urea nitrogen and creatinine. The expression of specific markers for podocytes, distal tubules (DTs), and CDs was detected in BXSB urine. Cells immunopositive for Wilms tumor 1 (podocyte marker) and interleukin-1 family, member 6 (damaged DT and CD marker) in the kidney significantly decreased and increased in BXSB versus B6, respectively. In the PCR array analysis of inflammatory cytokines and chemokines, Il10, Cxcl2, C3, and Il1rn showed relatively higher expression in BXSB kidneys than in B6 kidneys. In particular, the highest expression of C3 mRNA was detected in the urine from BXSB mice. Furthermore, C3 protein and mRNA were localized in the epithelia of damaged nephrons. These findings suggest that epithelial cells of the glomerulus, DT, and CD are dropped into the urine, and that these patterns are associated with renal pathology progression. We conclude that evaluation of urinary cellular patterns plays a key role in the early, noninvasive diagnosis of renal disease.
  • Ichii O, Otsuka S, Namiki Y, Hashimoto Y, Kon Y
    PloS one 6 (11) e27783  2011 [Refereed][Not invited]
  • Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abu Al Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shin-Hyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon
    VETERINARY RESEARCH COMMUNICATIONS 34 (6) 557 - 567 0165-7380 2010/08 [Refereed][Not invited]
    Previously, the distribution of myoepithelial cells (mecs) in the salivary glands was studied by both immunohistochemistry, and transmission electron microscopy; however, little was elucidated concerning their morphological features, especially in goats. This study was performed to investigate the correlation between the cytoarchitecture of the mecs in goat major salivary glands (parotid, mandibular, and sublingual glands) and the nature of the saliva secretion. The cytoarchitectural features of the mecs were examined by scanning and transmission electron microscopy as well as immunohistochemically. The secretory endpieces in the parotid gland are of the pure serous type, but in both the mandibular and sublingual glands they are of the mixed type. In all studied glands, the intercalated ducts were covered by mecs which, unlike the large stellate cells that surrounded the secretory endpieces, were spindle-shaped with few cytoplasmic processes. Interestingly, the mecs were found to bulge on the basal surfaces of the serous acini and intercalated ducts in all glands and to be in close contact to the seromucous tubules surface in the mandibular and sublingual glands forming a continuous network around it. In conclusion, the differences in the degree of development of the mecs as well as the number of their cytoplasmic processes may be correlated with the nature of the secretion and the number of the secretory granules. Thus these observations may have some relevance in the diagnosis of atrophy and pathogenic conditions of these glands.
  • Yaser Hosny Elewa, Mohammad Hafez Bareedy, Ahmed Awad Abuel-Atta, Osamu Ichii, Saori Otsuka, Tomonori Kanazawa, Shinhyo Lee, Yoshiharu Hashimoto, Yasuhiro Kon
    JAPANESE JOURNAL OF VETERINARY RESEARCH 58 (2) 121 - 135 0047-1917 2010/08 [Refereed][Not invited]
    The structural characteristics of the parotid glands in small ruminants (goat, sheep) were observed and compared to those of a major laboratory animal, the mouse. Their parotid glands consist of the purely serous type. Ultrastructurally, the serous acini of goats and sheep were characterized by the presence of well-developed basolateral expansions of folds, which are characteristics of electrolyte- and water-transporting epithelium. Moreover in ruminants, unlike the mouse, the presence of numerous intercellular canaliculi as well as microvilli projecting into both the intercellular canaliculi and the lumina of the serous acini provided a large surface area for osmotic equilibrium and isotonic saliva secretion. Most of the secretory granules in goats and sheep contained peripherally located inclusions that showed dense reaction products for acid phosphatase. This indicates that most of the secretory granules undergo lysosomal degradation rather than secretion. An apocrine mode of secretion of some secretory granules was occasionally observed in some acini of goats and sheep but only exocytotic features were observed in mice. In the goat, the serous acini showed three morphologically different types, which might be an indication of different activity phases. Furthermore, alpha-smooth muscle actin-, and vimentin-positive myoepithelial cells were observed only around the serous acini and the intercalated ducts. From these findings, we consider that the structural characteristics of ruminant parotid glands might reflect their physiological role in the copious isotonic saliva secretion with a low protein concentration.
  • O. Ichii, A. Kamikawa, S. Otsuka, Y. Hashimoto, N. Sasaki, D. Endoh, Y. Kon
    LUPUS 19 (8) 897 - 905 0961-2033 2010/07 [Refereed][Not invited]
    B6. MRLc1(82-100) congenic mice carrying the telomeric region of lupus-prone MRL chromosome 1 develop autoimmune glomerulonephritis (GN). The GN susceptibility locus of B6. MRLc1(82-100) contains the interferon activated gene 200 (Ifi200) family, which consists of Ifi202, 203, 204, and 205. Recently, Ifi202 was suggested as a candidate gene for murine lupus. In this study, we assessed the association between Ifi200 family and GN in several disease models. We compared the expression of Ifi200 family members in 24 organs between the C57BL/6 and B6. MRLc1(82-100). The expressions of Ifi200 family members differed between strains, and the most dramatic differences appeared in Ifi202 expression. Briefly, in the blood, immune organs, lungs, and testes mRNA expression was higher in B6. MRLc1(82-100) mice. In the kidney and immune organs, only Ifi202 expression increased with the development of GN in B6. MRLc1(82-100), and significant differences from C57BL/6 were observed even before disease onset. Ifi202 expression in the kidneys of BXSB, NZB/WF1, and MRL/lpr was also significantly high in the early- and late-disease stages. Furthermore, laser microdissection-reverse-transcriptase-polymerase chain reaction analysis confirmed the high Ifi202 expression in all areas of B6. MRLc1(82-100) kidneys. In conclusion, in the Ifi200 family, Ifi202 expressions in the kidney and immune organs significantly increased with GN progression. Lupus (2010) 19, 897-905.
  • Masataka Chihara, Saori Otsuka, Osamu Ichii, Yoshiharu Hashimoto, Yasuhiro Kon
    MOLECULAR REPRODUCTION AND DEVELOPMENT 77 (7) 630 - 639 1040-452X 2010/07 [Refereed][Not invited]
    The blood testis barrier (BTB) separates the seminiferous epithelium into the ad-luminal and basal compartments. During murine spermatogenesis, preleptotene/leptotene spermatocytes migrate from the basal to the adluminal compartment through the BTB during stages VIII-IX. In the present study, we focused on the tight junction (TJ) molecules and analyzed their spatiotemporal expression during the murine seminiferous epithelial cycle. Structural analysis revealed that the principal components of the BTB, for example, claudin-3, claudin-11, occludin, and zonula occludens-1 (ZO-1), were localized at the basal and luminal sides of the preleptotene/leptotene spermatocytes during the migration stages (VIII-IX). Although we detected claudin-11, occludin, and ZO-1 throughout spermatogenesis, claudin-3 was only detected during stages VI-IX. Quantitative PCR using dissected seminiferous tubules from three stages (Early: II-VI, Middle: VII-VIII, Late: IX-I) clarified that the mRNA levels of TJ molecules were not correlated with the histoplanimetrical protein levels during spermatogenesis. Additionally, tubulobulbar complexes, considered to be involved in the internalization of TJ, were observed at the BTB site. Furthermore, a significant reduction in the mRNA levels of genes for the degradation of occludin (Itch) and endocytic recycling (Rab13) were observed during the Late and Middle stages, respectively. Therefore, we hypothesized that the lag between mRNA and protein expression of TJ molecules may be due to posttranslational modulation, for example, tubulobulbar complexes and endocytic recycling processes. In conclusion, these findings indicate that the integrity of the BTB is maintained throughout spermatogenesis, and the stage-specific localization of claudin-3 protein plays an important role in regulating BTB permeability. Mol. Reprod. Dev. 77: 630-639, 2010. (C) 2010 Wiley-Liss, Inc.
  • Saori Otsuka, Yuka Namiki, Osamu Ichii, Yoshiharu Hashimoto, Nobuya Sasaki, Daiji Endoh, Yasuhiro Kon
    MAMMALIAN GENOME 21 (3-4) 153 - 161 0938-8990 2010/04 [Refereed][Not invited]
    MRL/MpJ (MRL) mouse testes have several unique characteristics, including the appearance of oocytes, the occurrence of metaphase-specific apoptosis of meiotic spermatocytes, and the presence of heat-shock-resistant spermatocytes. In the present study we used chromosomal mapping to determine the genomic background associated with small testis size in MRL mice. We prepared and analyzed C57BL/6-based congenic mice carrying MRL mouse loci. Quantitative trait loci (QTL) analysis revealed susceptibility loci for small testis size at 100 cM on chromosome (Chr) 1 and at around 80 cM on Chr 2. Analysis with B6.MRLc1 and B6.MRLc2 congenic mice and double-congenic mice confirmed the QTL data and showed that low testis weight in MRL mice was caused by germ cell apoptosis. Through histological examinations we found that B6.MRLc1 and B6.MRLc2 mice showed stage-specific apoptosis in their testes, the former at metaphase stage XII and the later at pachytene stage IV. Metaphase-specific apoptosis of spermatocytes occurs due to mutation of the exonuclease 1 (Exo1) gene located at 100 cM on Chr 1. Thus, the mutation of the Exo1 gene is also responsible for low testis weight caused by metaphase-specific apoptosis. In conclusion, testis weight is reduced in MRL mice due to apoptosis of germ cells caused by mutations in loci on Chrs 1 and 2.
  • Shin-hyo Lee, Osamu Ichii, Saori Otsuka, Yoshiharu Hashimoto, Yasuhiro Kon
    MAMMALIAN GENOME 21 (3-4) 162 - 171 0938-8990 2010/04 [Refereed][Not invited]
    MRL/MpJ (MRL) is a model mouse for autoimmune diseases such as dermatitis, vasculitis, arthritis, and glomerulonephritis. In addition to these immune-associated disorders, we found that older MRL mice develop ovarian cysts originating from the rete ovarii, which is lined by ciliated or nonciliated epithelium and considered remnants of mesonephric tubules. Ovarian cysts, which are reported to have several sources, are associated with female infertility, but information regarding the genetic etiology of ovarian cysts originating from the rete ovarii is rare. In this study, to elucidate the genetic background of development of ovarian cysts, we performed quantitative trait locus (QTL) analysis using 120 microsatellite markers, which cover the whole genome of murine chromosomes, and 213 backcross progenies between female MRL and male C57BL/6N mice. The quantitative trait measured was the circumferences of rete ovarii or ovarian cysts. As a result, suggestive linkages were detected on Chrs 3, 4, 6, and 11, but significant linkages were located on Chr 14 by interval mapping. We thereby designated the 27.5-cM region of Chr 14 "MRL Rete Ovarian Cysts (mroc)." The peak regions of Chrs 4 and 14 in particular showed a close additive interaction (p < 0.00001). From these results we concluded that multiple loci on Chrs 3, 4, 6, 11, and 14 interact to result in development of ovarian cysts in MRL mice.
  • Osamu Ichii, Saori Otsuka, Nobuya Sasaki, Akira Yabuki, Hiroshi Ohta, Mitsuyoshi Takiguchi, Yoshiharu Hashimoto, Daiji Endoh, Yasuhiro Kon
    LABORATORY INVESTIGATION 90 (3) 459 - 475 0023-6837 2010/03 [Refereed][Not invited]
    Identification of factors that exacerbate a disease is important for the development of biomarkers. In this study, we discovered ectopic overexpression of interleukin-1 family, member-6 (IL-1F6) in several murine renal diseases. IL-1F6 participates in cytokine/chemokine production in the epithelium. In PCR array analysis for inflammatory mediators, Il1f6 showed the highest expression in the kidney of the B6. MRLc1 glomerulonephritis model. IL-1F6 was localized in the epithelium from the DCTs to CCDs, which showed tubular dilations or epithelial deciduations. Ultrastructual examination of the epithelial cells revealed that IL-1F6 was localized on the cytoplasmic ribosome, vesicles, and nucleus. In and around these tubules, we found infiltrations of CD3-positive T-cells and nestin- or alpha-smooth-muscle actin-positive mesenchymal cells. Expression of the IL-1F6 protein and Il1f6 mRNA in the kidney was increased by the development of TILs in the B6. MRLc1 model and in lupus (BXSB, NZB/WF1, and MRL/lpr), nephrotic syndrome (ICGN), and streptozotocin-induced diabetic models. IL-1F6 was also detected in the epithelia having squamous or deciduous contours in other organs such as the skin, esophagus, thymus, or uterus. In vitro analysis using M-1 cells from the murine collecting duct revealed that Il1f6 mRNA induction was related to the upregulation of IL-6, TGF-beta receptor-1, and mesenchymal markers and to the downregulation of epithelial markers and changes in the squamous cells of the epithelium. Interestingly, urine Il1f6 mRNA expression was detected earlier than renal dysfunctions in these mouse models. Ectopic overexpression of IL-1F6 in kidneys is associated with TILs and especially with cell infiltrations and changes in epithelial morphology. We propose that local overexpression of IL-1F6 is related to the development of TILs.
  • Teppei Ikeda, Tomonori Kanazawa, Saori Otsuka, Osamu Ichii, Yoshiharu Hashimoto, Yasuhiro Kon
    JOURNAL OF VETERINARY MEDICAL SCIENCE 71 (9) 1161 - 1168 0916-7250 2009/09 [Refereed][Not invited]
    The caspases (Casps) are a family of cysteine proteases that are known to regulate apoptotic signaling. Apoptosis by activation of Casp is strongly associated with embryonal development and regeneration in many organs, therefore indicating that disorders caused by homozygous mutation in Casp genes can result in embryonic lethality. In the present study, the authors investigated the causative relationship between skeletal myogenesis and the activation of Casps by analyzing their dynamics during Mouse embryogenesis. Individual myogenetic tissues were obtained from C57BL/6 Mouse embryos aged 12.5-17.5 days post-conception (dpc), and the expression of Casps was analyzed by histochemical and molecular biological methods. Immunoreactions for Casp-3, -9 and -12 were detected first in myoblasts, increasing according to embryonal development, as a result Of Which myoblasts differentiated into myotube cells. On the other hand, the immunoreaction for ssDNA, which is well-known as an apoptosis marker, was little detected during the skeletal myogenesis. Quantification analysis for Casp mRNA expression by RT-PCR as well as by in situ hybridization showed a peak at 15.5 dpc but a decrease at 17.5 dpc. Similar dynamics were detected for Myod1 mRNA, one of the Muscle regulatory factors, but not for Fast, Bax and Rock1, apoptosis-associated factors during skeletal myogenesis. These results Suggest that the activation of Casps in skeletal myogenesis is deeply associated with myoblast differentiation, but not directly related to apoptosis.
  • Akihiro Kamikawa, Osamu Ichii, Daisuke Yamaji, Takeshi Imao, Chihairu Suzuki, Yuko Okamatsu-Ogura, Akira Terao, Yasuhiro Kon, Kazuhiro Kimura
    DEVELOPMENTAL DYNAMICS 238 (5) 1092 - 1099 1058-8388 2009/05 [Refereed][Not invited]
    Mammary glands develop postnatally in response to the hypothalamic-pituitary-gonadal axis. Obesity-induced changes in the local environment, however, retard mammary gland development during late pregnancy and lactation. To clarify the effects of obesity on fundamental duct development, we compared the mammary glands of nulliparous nonpregnant obese mice fed a high-fat diet with those of lean mice fed a normal diet. Obese mice had enlarged mammary glands, reflecting fat pad size, whereas the ducts in obese mice showed a less dense distribution with less frequent branching. Additionally, the ducts were surrounded by thick collagen layers, and were incompletely lined with myoepithelium. Because leptin receptors were localized in the epithelium region and leptin that was highly expressed in the obese glands suppressed mammary epithelial cell proliferation in vitro, the present results suggest that obesity disrupts mammary ductal development, possibly by remodeling the mammary microenvironment and promoting the expression of such paracrine factors as leptin. Developmental Dynamics 238:1092-1099, 2009. (C) 2009 Wiley-Liss, Inc.
  • O. Ichii, A. Konno, N. Sasaki, D. Endoh, Y. Hashimoto, Y. Kon
    LUPUS 18 (6) 491 - 500 0961-2033 2009/05 [Refereed][Not invited]
    Female B6. MRLc1(82-100) congenic mice develop more severe autoimmune glomerulonephritis (AGN) than males. We assessed the effects of gonadectomy on the pathogenesis of AGN in these mice. One-month-old male and female mice were divided into sham-operated group (SG) and gonadectomized group (GG), and the pathological changes were investigated at 8 months. SG females showed higher spleen and thymus weights, serum total IgG and autoantibody levels, glomerular damage scores and percent IgG- and CD3-positive glomeruli as compared with SG males. Gonadectomy showed more remarkable effects in males than in females. Spleen and thymus weights, urinary albumin excretion, glomerular damage scores, percent IgG- and CD3-positive glomeruli, and CD3-positive areas in the spleen were significantly higher in GG males than in SG males. CD3-positive cells were observed in both the thymic cortex and medulla in all animals except SG males. The expression ratio of active Fc gamma receptor (Fcgr) 3 to inhibitory Fcgr2b in the kidneys, which we have previously demonstrated to have a great impact on pathogenesis in B6. MRLc1(82-100), was significantly higher in GG males than in SG males. These results suggested that the differences in the pathogenesis of AGN are primarily because of the inhibitory roles of the male sex hormones. Lupus (2009) 18, 491-500.
  • Keisuke Hino, Saori Otsuka, Osamu Ichii, Yoshiharu Hashimoto, Yasuhiro Kon
    JAPANESE JOURNAL OF VETERINARY RESEARCH 57 (1) 3 - 11 0047-1917 2009/05 [Refereed][Not invited]
    Hydrocephalus is an intractable disease characterized by the excessive accumulation of cerebrospinal. fluid (CSF) in the cerebral ventricles. There are many cases in both human and animals; however, the cause and mechanism of it's development is not clearly understood. In this study, differences of cerebral ventricles in 5 inbred mice strains (MRL/MpJ, C57BL/6, C3H/He, DBA/2 and BALB/c) were investigated. by histological techniques to determine the possibility of a new animal model for hydrocephalus. Our analysis showed that significant differences in the volume and the surface area of lateral ventricles in the 5 inbred strains, with MRL/MpJ mice having the largest lateral, third, aqueduct and fourth ventricles. In addition, when MRL/MpJ mice were compared to BALB/c mice on 0 day after birth, the former already had larger lateral ventricles than the latter. Although there were no significant difference in the ratios of ependymal cell types in MRL/MpJ mice and BALB/c mice, the number and the diameter of lipid droplets in MRL/MpJ mice were, interestingly, smaller than those in BALB/c mice. It is well known that ependymal cells absorb nutritional substances in CSF by endocytosis, suggesting the possibility that their decrease may relate to the larger cerebral ventricles in MRL/MpJ. In conclusion, MRL/MpJ mice have greater volumes in cerebral ventricles than other strains and may be useful for a model showing high susceptibility to hydrocephalus.
  • Ichii O, Konno A, Sasaki N, Endoh D, Hashimoto Y, Kon Y
    Kidney international 74 (3) 339 - 347 0085-2538 2008/08 [Refereed][Not invited]
  • Ichii O, Konno A, Sasaki N, Endoh D, Hashimoto Y, Kon Y
    Histology and histopathology 23 (4) 411 - 422 0213-3911 2008/04 [Refereed][Not invited]
  • Ichii O, Yabuki A, Ojima T, Matsumoto M, Taniguchi K, Suzuki S
    Histology and histopathology 23 (2) 143 - 150 0213-3911 2008/02 [Refereed][Not invited]
  • Akira Yabuki, Satoshi Taharaguchi, Osamu Ichii, Masayasu Kojima, Yoshihiro Nishi, Hiroharu Mifune, Ryozo Kamimura, Mitsuharu Matsumoto, Shusaku Suzuki
    HISTOCHEMISTRY AND CELL BIOLOGY 126 (2) 231 - 238 0948-6143 2006/08 [Refereed][Not invited]
    Ghrelin is a novel peptide hormone, originally identified in the rat and human stomach that plays various important roles. In the present study, we report the intra-renal localization of ghrelin in laboratory rodents. Kidneys from 3 month-old mice, rats and hamsters of both sexes were analyzed by immunohistochemistry. Positive signals were clearly observed in the epithelium of the distal tubules, whereas other segments of the nephron or interstitial cells, including juxtaglomerular cells, showed negative reactions. Preembedding immunoelectron microscopy revealed positive signals exclusively on the basolateral membrane in the distal tubular cells and in the collecting ducts. In addition, prepro-ghrelin gene expression was assessed by RT-PCR, and the expected 329-bp prepro-ghrelin mRNA was clearly detected in the kidney. On Western blot analysis, although a specific band for ghrelin (3 kDa) was not detected in the kidney, the expected band for prepro-ghrelin (13 kDa) was clearly detected in both the stomach and the kidney. This paper clarified the intra-renal localization of ghrelin.
  • O Ichii, A Yabuki, T Ojima, M Matsumoto, S Suzuki
    JOURNAL OF VETERINARY MEDICAL SCIENCE 68 (5) 439 - 445 0916-7250 2006/05 [Refereed][Not invited]
    In the present study, we histologically and morphometrically investigated species differences in renal structure using laboratory rodents (mice, gerbils, hamsters, rats, and guinea pigs). Morphometric parameters were as follows, 1) diameter of the cortical renal corpuscles, 2) diameter of the juxtamedullary renal corpuscles, 3) percentage of the renal corpuscles with a cuboidal parietal layer, 4) number of nuclei in proximal convoluted tubules (PCTs) per unit area of cortex. 5) semi-quantitative score of the periodic acid-Schiff (PAS) positive granules in PCTs, and 6) semi-quantitative score of the PAS-positive granules in proximal straight tubules (PSTs). Significant species differences were detected for each parameter, and particularly severe differences were observed in the PAS-positive granules of PCTs and PSTs. Granular scores varied among species and sexes. Vacuolar structures that did not stain with PAS or hematoxylin-eosin were observed in the renal proximal tubules. The appearance and localization of these vacuolar structures differed remarkably between species and sexes.

Books etc

  • 牛の乳房炎
    日本乳房炎研究会編 (Joint work第3章菌がつくるバイオフィルムとは)
    緑書房 2018/11
  • 獣医組織学第7版
    日本獣医解剖学会編 (Contributor第12章「腎臓」、第19章「家禽の組織学」)
    学窓社 2017/03
  • カラーアトラス獣医解剖学第2版
    カラーアトラス獣医解剖学編集委員会 (Joint translation第12章「鳥類の解剖学」)
    緑書房 2016/03
  • 猫の解剖 カラーリングアトラス
    九郎丸正道監修 (Joint translation「泌尿器」、「呼吸器」)
    学窓社 2014
  • 獣医組織学第6版
    日本獣医解剖学会編 (Contributor第12章「腎臓」、第19章「家禽の組織学」)
    学窓社 2014
  • 小動物の実践歯科学
    Brool A. Niemiec (Joint translation第1章 解剖学と生理学)
    緑書房 2013/03
  • Annual Review 腎臓
    富野康日己ら編 (ContributorC分子生物学 腎臓病のmiRNA解析)
    中外医学社 2013/01
  • 獣医解剖・組織・発生学
    日本獣医解剖学会編 (Contributor獣医解剖学 第10章 泌尿器系)
    学窓社 2012/05
  • 獣医組織学第5版
    日本獣医解剖学会編 (Contributor第12章「腎臓」)
    学窓社 2011/03

Conference Activities & Talks

  • ネコの甲状腺機能に対するポリ塩化ビフェニル(PCBs)の影響評価〜甲状腺ホルモンの脱ヨード化と代謝能の解析  [Not invited]
    水川葉月, 高居名菜, 横山望, 市居修, 滝口満喜, 野見山桂, 高口倖暉, 西川博之, 池中良徳, 中山翔太, Tsend-ayush Sainnoxoi, 田辺信介, 石塚真由美
    第44回日本毒性学会  2017/07
  • イエネコのin vivo長期曝露試験:デカブロモジフェニルエーテ (BDE209)の生体内変化  [Not invited]
    田中啓介, 野見山桂, 水川葉月, 高口倖暉, 田上瑠美, Aksorn Saengtienchai,Tsend-ayush Sainnoxoi, 横山望, 市居 修, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介
    第26回環境化学討論会  2017/06
  • PCBs曝露 がイヌ・ネコの甲状腺ホルモン恒常性へ及ぼす影響  [Not invited]
    高口 倖暉, 野見山 桂, 西川 博之, 水川 葉月, 田上 瑠美, 芳之内 結加, 横山 望, 市居 修, 滝口満喜, 中山 翔太, 池中良徳, 石塚真由美, 岩田久人, 国末達也, 田辺信介
    第26回環境化学討論会  2017/06
  • 血清中メタボローム解析によるイエネコのPCBs毒性影響評価  [Not invited]
    野見山桂, 西川 博之, 水川葉月, 高口倖暉, Tsend-ayush Sainnoxoi, 横山 望, 市居 修, 滝口満喜, 石塚真由美, 池中良徳, 中山翔太, 江口哲史, 国末達也, 田辺信介
    第26回環境化学討論会  2017/06
  • ポリ塩化ビフェニル(PCBs)暴露によるネコ甲状腺機能への影響評価 〜 甲状腺ホルモンの脱ヨード化と代謝能解析〜  [Not invited]
    水川葉月, 高居名菜, 横山望, 市居修, 滝口満喜, 野見山桂, 高口倖暉, 西川博之, 池中良徳, 中山翔太, Tsend-ayush Sainnoxoi, 田辺信介, 石塚真由美
    第26回環境化学討論会  2017/06
  • ウシ生体内で形成させた移植医療用組織の構造  [Not invited]
    今山知佳, 鈴木貴弘, 小林 謙, 三谷朋弘, 市居 修, 小千田圭吾, 池田哲平, 寺澤 武, 中山泰秀
    日本畜産学会第122回大会  2017/03
  • 家畜生体内を利用して再生移植医療用組織をつくる  [Not invited]
    西邑隆徳, 今山知佳, 鈴木貴弘, 小林 謙, 三谷朋弘, 市居 修, 小千田圭吾, 池田哲平, 寺澤 武, 中山泰秀
    日本畜産学会第122回大会  2017/03
  • RNAから展開する腎臓病研究 〜 獣医臨床へのアプローチ〜  [Invited]
    市居 修
    第13回日本獣医内科学アカデミー 学術大会  2017/02
  • 腎臓病を知らせる microRNA −病態マーカーとしての可能性と問題点−  [Invited]
    市居 修
    第33回日本毒性病理学会学術集会  2017/01
  • 生体内組織形成術による管状組織体の壁厚制御  [Not invited]
    寺澤 武, 西邑 隆徳, 三谷 朋弘, 市居 修, 中山 泰秀
    第54回日本人工臓器学会大会  2016/11
  • Characteristic for biotransformation of polychrolinated biphenyls in cats  [Not invited]
    Hazuki Mizukawa, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Kei Nomiyama, Hiroyuki Nishikawa, Yoshinori Ikenaka, Shouta M.M. Nakayama, Kohki Takaguchi, Shinsuke Tanabe, Mayumi Ishizuka
    The 7th SETAC World Congress/37th SETAC North America Annual Meeting  2016/11
  • ウシの咽頭扁桃は鼻腔から投与した黄色ブドウ球菌死菌に対する免疫応答の場となる  [Not invited]
    長澤 裕哉, 菊 佳男, 田邉 扶由子, 菅原 和恵, 石川 義春, 市居 修, 昆 泰寛, 門田 耕一, 林 智人
    第21回日本乳房炎研究会・学術集会  2016/10
  • In vivo analysis of PCB metabolic capacities and effects on the thyroid hormone in cats  [Not invited]
    Hazuki, Mizukawa, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Kei Nomiyama, Hiroyuki Nishikawa, Kohki Takaguchi, Aksorn Saengtienchai, Tsend-ayush Sainnoxoi, Yoshinori Ikenaka, Shouta M.M. Nakayama, Shinsuke Tanabe, Mayumi Ishizuka
    The 9th International PCB Workshop  2016/10
  • コットンラットの咽頭喉頭部,甲状腺及びその周囲組織にみられる形態学的特徴  [Not invited]
    中村 鉄平, 入江 隆夫, 市居 修, 篠原 明男, 孝口 裕一, 越本 知大, 長崎 健一, 昆 泰寛
    日本解剖学会第62回東北・北海道連合支部学術集会  2016/09
  • マウス十二指腸空腸曲の形態形成機序の解析  [Not invited]
    尾之内佐和, 市居 修, 昆 泰寛
    日本解剖学会第62回東北・北海道連合支部学術集会  2016/09
  • 自己免疫疾患が卵管の卵子捕捉機能に及ぼす影響について  [Not invited]
    細谷 実里奈, 市居 修, 中村 鉄平, Yaser Hosny Ali Elewa, 昆 泰寛
    日本解剖学会第62回東北・北海道連合支部学術集会  2016/09
  • 遠位尿細管上皮細胞の形態機能を制御するIL-1F6/IL-36α  [Not invited]
    居 修, 中村鉄平, 岡村匡史, 木村純平, 堀野太郎, 昆 泰寛
    日本解剖学会第62回東北・北海道連合支部学術集会  2016/09
  • Effect of H2S on 5-HT release from glomus cells in the chicken thoracic aorta  [Not invited]
    Dugar DELGERMURUN, 山口 聡一郎, 市居 修, 昆 泰寛, 伊藤 茂男, 乙黒 兼一
    第159回 日本獣医学会学術集会  2016/09
  • 抗ワクモ(Dermanyssus gallinae)ワクチン開発に向けたワクモ由来フェリチン2の性状解析  [Not invited]
    伊勢崎 政美, 村田 史郎, 酒井 英史, 矢吹 卓也, 種子野 章, 市居 修, 伊東 拓也, 今内 覚, 大橋 和彦
    第159回 日本獣医学会学術集会  2016/09
  • 芳香族炭化水素受容体シグナルの活性化は胃粘膜異常を増悪する  [Not invited]
    團塚 愛, Annika Hanberg, 市居 修, 中村 鉄平, 昆 泰寛
    第159回 日本獣医学会学術集会  2016/09
  • マウス遠位尿細管の嚢胞形成に関与する新規原因遺伝子座の役割  [Not invited]
    市居 修, 中村 鉄平, 矢吹 映, 堀野 太郎, 昆 泰寛
    第159回 日本獣医学会学術集会  2016/09
  • ウシ咽頭扁桃は鼻腔投与した黄色ブドウ球菌に対する免疫応答の場になる  [Not invited]
    長澤 裕哉, 菊 佳男, 田邉 扶由子, 菅原 和恵, 石川 義春, 野地 智法, 市居 修, 昆 泰寛, 麻生 久, 門田 耕一, 林 智人
    第159回 日本獣医学会学術集会  2016/09
  • Histopathological correlations between the mediastinal fat associated lymphoid clusters and bleomycin-induced pneumonitis in mice  [Not invited]
    Y. H. A. Elewa, Md. A. Masum, T. Nakamura, O. Ichii, Y. Kon
    第159回 日本獣医学会学術集会  2016/09
  • CD34-positive capillary decreased with the progression of kidney disease in mouse models  [Not invited]
    Masum Md. Abdul, Elewa YH, 市居 修, 昆 泰寛
    第159回 日本獣医学会学術集会  2016/09
  • 自己免疫疾患モデルMRL/MpJ-Faslprマウスにみられる卵子のキャッチアップ障害  [Not invited]
    細谷 実里奈, 市居 修, 中村 鉄平, Yaser Hosny Ali Elewa, 昆 泰寛
    第159回 日本獣医学会学術集会  2016/09
  • マウス胎 子腸管器官培養法により形成された十二指腸空腸曲の解析  [Not invited]
    尾之内佐和, 市居 修, 昆 泰寛
    第159回 日本獣医学会学術集会  2016/09
  • コットンラットにおけるインスリン抵抗性と脂肪蓄積との関連  [Not invited]
    中村 鉄平, 市居 修, 入江 隆夫, 寸田 祐嗣, 孝口 裕一, 長崎 健一, 吉安 友二, 昆 泰寛
    第159回 日本獣医学会学術集会  2016/09
  • 犬と猫の慢性腎臓病における尿細管周囲毛細血管の変化  [Not invited]
    中村麗菜, 矢吹 映, 市居 修, 水川葉月, 横山 望, 大和 修
    第159回 日本獣医学会学術集会  2016/09
  • Activation of Ahr signaling pathway aggravates the mucosal abnormality in stomach  [Not invited]
    Ai Dantsuka, Annika Hanberg, Osamu Ichii, Yasuhiro Kon
    The 4th Sapporo Summer Seminar for One Health  2016/09
  • CD34-positive capillary decreased with the progression of kidney disease in mice  [Not invited]
    Masum Md. Abdul, Elewa YH, Ichii O, Kon Y
    The 4th Sapporo Summer Seminar for One Health  2016/09
  • Analysis of the mouse duodenojejunal flexure using the fetal gut organ culture system  [Not invited]
    Onouchi S, Ichii O, Kon Y
    The 4th Sapporo Summer Seminar for One Health  2016/09
  • The effect of environmental pollutants to pet animals ~Level and effects of Persistent organic pollutants (POPs) to domestic ca  [Not invited]
    Tsend-ayush Sainnokhoi, Hazuki Mizukawa, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Kei Nomiyama, Aksorn Saengtienchai, Shinsuke Tanabe, Yoshinori Ikenaka, Shouta M.M. Nakayama, Mayumi Ishizuka
    The 4th Sapporo Summer Seminar for One Health  2016/09
  • イヌの尿中exosomeに含まれるマイクロRNA - 病態マーカーとしての可能性 ?  [Not invited]
    市居修, 大田寛, 堀野太郎, 中村鉄平, 細谷実里奈, 溝口達也, 森下啓太郎, 中村健介, 星野有希, 高木哲, 佐々木東, 滝口満喜, 佐藤遼, 小山田和央, 昆泰寛
    第9回 日本獣医腎泌尿器学会学術集会  2016/08
  • 雌性コットンラット(Sigmodon hispidus)にみられる腎性貧血  [Not invited]
    中村 鉄平, 市居 修, 入江 隆夫, 孝口 裕一, 寸田 祐嗣, 堀野 太郎, 昆 泰寛
    第9回 日本獣医腎泌尿器学会学術集会  2016/08
  • Metabolic capacities of polychlorinated biphenyls (PCBs) in cats and dog  [Not invited]
    Hazuki Mizukawa, Kei Nomiyama, Shinsuke Tanabe, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Yoshinori Ikenaka, Shouta M.M. Nakayama, Mayumi Ishizuka, M
    The 8th international Toxicology symposium in Africa  2016/08
  • ポリ塩化ビフェニル(PCBs)のin vivo暴露によるネコの異物代謝解明と甲状腺ホルモンへの影響評価  [Not invited]
    水川 葉月, 前原 美咲, 横山 望, 市居 修, 滝口 満喜, 野見山 桂, 西川 博之, 池中 良徳, 中山 翔太, 高口 倖暉, 田辺 信介, 石塚 真由美
    第43回日本毒性学会学術年会  2016/06
  • メタボローム解析を用いたPCBsによるイエネコの毒性影響評価  [Not invited]
    西川博之, 野見山桂, 水川葉月, 横山望, 市居修, 滝口満喜, 石塚真由美, 池中良徳, 中山翔太, 江口哲史, 国末達也, 田辺信介
    第25回環境化学討論会  2016/06
  • ネコにおけるポリ塩化ビフェニル(PCBs)の異物代謝機構解明と甲状腺ホルモンへの影響評価  [Not invited]
    水川葉月, 前原美咲, 横山望, 市居修, 滝口満喜, 野見山桂, 西川博之, 池中良徳, 中山翔太, 高口倖暉, 田辺信介, 石塚真由美
    第25回環境化学討論会  2016/06
  • Mouse duodenojejunal flexure formation with asymmetric morphologies between the inner and outer bending sides  [Not invited]
    Onouchi S, Ichii O, Kon Y
    JSDB Special Symposium: Frontier of Developmental Biology Hosted by JSDB  2016/06
  • SEM法を利用した腎生検の迅速電子顕微鏡診断への応用  [Not invited]
    髙木 孝士, 城 謙輔, 大野 伸彦, 齊藤 成, Thai Quynh T, 昆 泰寛, 市居 修, Yeser Hosny Ali Elewa H, 笹野 公伸
    第105回日本病理学会総会  2016/05
  • Immune system via novel mediastinal fat associated lymphoid clusters in mice  [Not invited]
    Y. H. A. Elewa, O. Ichii, Y. Kon
    The Scientific Symposium  2016/03
  • Sex-related difference of the mediastinal fat associated lymphoid clusters in MRL/MpJ-Faslpr autoimmune disease model mice.  [Not invited]
    Y. H. A. Elewa, O. Ichii, Y. Kon
    The 11th Scientific Vet. Med. (second international) conference  2016/03
    Hazuki Mizukawa, Misaki Maehara, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Kei Nomiyama, Yoshinori Ikenaka, Shouta M.M.Nakayama, Shinsuke Tanabe, Mayumi Ishizuka
  • Metabolism and biotransformation of organohalogen compounds in the liver microsomes of cats and dogs  [Not invited]
    Hazuki Mizukawa, Kei Nomiyama, Nozomu, Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Yoshinori Ikenaka, Shouta M.M, Nakayama, Misaki Maehara, Shinsuke Tanabe, Mayumi Ishizuka
    SETAC North America 36th Annual Meeting  2015/11
  • ミニチュア・ダックスフンドの炎症性結直腸ポリープ症例の結直腸粘膜におけるToll-like receptor 2,4の局在解析  [Not invited]
    横山 望, 大田 寛, 賀川 由美子, 山崎 淳平, 市居 修, Nisa Khoirun, 森田 智也, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 中村 健介, 滝口 満喜
    第158回 日本獣医学会学術集会  2015/09
  • マウス十二指腸空腸曲の細胞外基質は屈曲形成と共に変遷する  [Not invited]
    尾之内佐和, 市居 修, 昆 泰寛
    第158回 日本獣医学会学術集会  2015/09
  • 日本獣医学会学術集会 遠位尿細管傷害を知らせるマーカー分子“IL-1F6/IL-36a”の有用性  [Not invited]
    市居 修, 中村 鉄平, 堀野 太郎, 木村 純平, 岡村 匡史, 昆 泰寛
    第158回 日本獣医学会学術集会  2015/09
  • Gut morphogenesis in mice ?spatiotemporal distribution of the extracellular matrix changes during duodenojejunal flexure formation  [Not invited]
    Onouchi S, Ichii O, Kon Y
    The 3rd Sapporo Summer Seminar for One Health  2015/09
  • 尿中exosome由来microRNAの解析−動物種横断的腎障害マーカーになるか?−  [Not invited]
    市居修, 大田寛, 堀野太郎, 中村鉄平, 細谷実里奈, 溝口達也, 森下啓太郎, 中村健介, 佐々木東, 滝口満喜, 佐藤遼, 小山田和央, 昆泰寛
    第8回 日本獣医腎泌尿器学会学術集会  2015/08
  • Interleukin 1 family, member 6 is a useful histopathological diagnostic marker in acute kidney injury  [Not invited]
    O. Ichii, D. Shiozuru, S. Otsuka-Kanazawa, Y. Kon
    The 5th Congress of the Asian Association of Veterinary Anatomists  2015/02
  • Biased distribution of ovarian mast cells alter the early follicular development in postnatal MRL/MpJ mice  [Not invited]
    T. Nakamura, O. Ichii, S. Otsuka-Kanazawa, K. Nagasaki, Y. Kon
    The 5th Congress of the Asian Association of Veterinary Anatomists  2015/02
  • A novel mouse mediastinal fat-associated lymphoid tissue and its relationship with autoimmune disease  [Not invited]
    Y. H.A. Elewa, S. Otsuka-Kanazawa, O. Ichii, Y. Kon
    The 5th Congress of the Asian Association of Veterinary Anatomists  2015/02
  • Autosomal causative locus for production of testicular oocytes in MRL/MpJ mice  [Not invited]
    Saori Otsuka-Kanazawa, Osamu Ichii, Yasuhiro Kon
    The 5th Congress of the Asian Association of Veterinary Anatomists  2015/02
  • Validation of the function of MRL/MpJ mouse-derived loci in the spermatogenesis under testicular hyperthermia  [Not invited]
    M. Chihara, S. Otsuka, O. Ichii, Y. Kon
    The 5th Congress of the Asian Association of Veterinary Anatomists  2015/02
  • Spatiotemporal distribution of the extracellular matrix in the fetal mouse duodenojejunal flexure  [Not invited]
    S. Onouchi, O. Ichii, S. Otsuka-Kanazawa, Y. Kon
    The 2nd Sapporo Summer Seminar for One Health  2015/02
  • Greb1, a Gene Responsible for the Development of Renal Cysts Originating in the Distal Tubules in DBA/2 Mice  [Not invited]
    Osamu Ichii, Saori Otsuka, Akira Yabuki, Taro Horino, Teppei Nakamura, Yasuhiro Kon
    American Society of Nephrology  2014/11
  • Toll-Like Receptor 8 Contributes to Podocyte Injury in Murine Autoimmune Glomerulonephritis  [Not invited]
    Junpei Kimura, Osamu Ichii, Teppei Nakamura, Taro Horino, Saori Otsuka, Yasuhiro Kon
    American Society of Nephrology  2014/11
  • 足細胞の機能形態を制御するmiR-26a −糸球体傷害のバイオマーカー核酸になり得る−  [Not invited]
    市居 修, 大塚沙織, 中村鉄平, 木村 純平, 堀野 太郎, 昆 泰寛
    第7回日本獣医腎泌尿器学会学術集会  2014/09
  • miR-26a − 腎糸球体上皮細胞の機能形態を制御する短鎖RNA  [Invited]
    市居 修
    第157回 日本獣医学会学術集会 日本獣医解剖学会シンポジウム  2014/09
  • Characterization of mouse mediastinal fat-associated lymphoid clusters (english)  [Not invited]
    Yaser Hosny Ali Elewa, 市居 修, 大塚 沙織, 昆 泰寛
    第157回 日本獣医学会学術集会  2014/09
  • Greb1 −DBA/2Crマウスに出現する遠位尿細管由来嚢胞の原因遺伝子候補−  [Not invited]
    市居 修, 大塚 沙織, 矢吹 映, 堀野 太郎, 中村 鉄平, 昆 泰寛
    第157回 日本獣医学会学術集会  2014/09
  • 自己免疫疾患モデルMRL/MpJ-lprマウスの卵巣は機能形態異常を示す  [Not invited]
    大谷 祐紀, 市居 修, 大塚 沙織, 中村 鉄平, 千原 正尚, 昆 泰寛
    第157回 日本獣医学会学術集会  2014/09
  • マウス十二指腸空腸曲における屈曲内−外側の形態学的差異  [Not invited]
    尾之内 佐和, 市居 修, 大塚 沙織, 昆 泰寛
    第157回 日本獣医学会学術集会  2014/09
  • 腎障害時にみられるMRL/MpJマウスの特別な修復過程について  [Not invited]
    塩水流 大地, 市居 修, 中村 鉄平, 大塚 沙織, 昆 泰寛
    第157回 日本獣医学会学術集会  2014/09
  • Toll-like receptor 8は自己免疫性糸球体腎炎の足細胞傷害に関与する  [Not invited]
    木村 純平, 市居 修, 大田 寛, 中村 鉄平, 堀野 太郎, 大塚 沙織, 昆 泰寛
    第157回 日本獣医学会学術集会  2014/09
  • 新生子MRL/MpJマウスにおける卵巣内肥満細胞の由来?卵巣-卵巣采結合部から出現する可能性?  [Not invited]
    中村 鉄平, 千原 正尚, 市居 修, 大塚 沙織, 長崎 健一, 昆 泰寛
    第157回 日本獣医学会学術集会  2014/09
  • MRL/MpJマウスに出現する精巣内卵細胞のエピゲノム解析  [Not invited]
    大塚 沙織, 市居 修, 昆 泰寛
    第157回 日本獣医学会学術集会  2014/09
  • Toll-like receptor 8 contributes to podocyte injury in murine autoimmune glomerulonephritis  [Not invited]
    Junpei Kimura, Osamu Ichii, Saori Otsuka, Yasuhiro Kon
    The 2nd Sapporo Summer Seminar for One Health  2014/09
  • 腎障害モデルにおける腎組織修復過程の観察 −MRL/MpJマウスが具備する創傷治癒形質との関連−  [Not invited]
    塩水流大地, 市居 修, 中村鉄平, 大塚沙織, 昆 泰寛
    第7回日本獣医腎泌尿器学会学術集会  2014/08
  • 伴侶動物の腎臓におけるToll-like receptor8の発現解析 -糸球体足細胞傷害に関与するバイオセンサー-  [Not invited]
    木村 純平, 市居 修, 大田 寛, 横山 望, 森下 啓太郎, 星野 有希, 高木 哲, 大塚 沙織, 昆 泰寛
    第7回日本獣医腎泌尿器学会学術集会  2014/08
  • The candidate factors for the development of chronic kidney disease.  [Not invited]
    Osamu Ichii, Saori Otsuka, Yasuhiro Kon
    The 16th SNU-HU Symposium Current Advances in Veterinary Medicine.  2013/12
  • MRL/MpJマウスに出現する肥満細胞  [Not invited]
    中村鉄平, 市居 修, 大塚沙織, 昆 泰寛
    日本解剖学会第59回東北・北海道連合支部学術集会  2013/09
  • マウスにおける十二指腸空腸曲形成機序の解析  [Not invited]
    尾之内佐和, 市居 修, 大塚沙織, 昆 泰寛
    日本解剖学会第59回東北・北海道連合支部学術集会  2013/09
  • 伴侶動物の腎臓に発現するmiRNAのデータベース構築−動物種共通のバイオマーカー開発を目指して  [Not invited]
    市居 修, 大塚沙織, 矢吹 映, 大田 寛, 堀野太郎, 昆 泰寛
    第156回 日本獣医学会学術集会  2013/09
  • 慢性膵炎の系統差に関する研究-MRLマウス1番染色体テロメア領域の影響  [Not invited]
    岡田祐樹, 市居 修, 大塚 沙織, 昆 泰寛
    第156回 日本獣医学会学術集会  2013/09
  • MRL/MpJマウスの卵細胞発育を制御する遺伝学的因子  [Not invited]
    山下由真, 市居 修, 大塚沙織, 昆 泰寛
    第156回 日本獣医学会学術集会  2013/09
  • ビタミンA欠乏食給餌マウスからみる精細胞−血液精巣関門の相互作用  [Not invited]
    千原正尚, 市居 修, 大塚沙織, 昆 泰寛
    第156回 日本獣医学会学術集会  2013/09
  • マウス消化管の発生に関する研究 〜どうして腸管は曲がるのか?〜  [Not invited]
    尾之内 佐和, 市居 修, 大塚 沙織, 橋本 善春, 昆 泰寛
    第154回 日本獣医学会学術集会  2013/09
  • The uremic toxin indoxyl sulfate causes podocyte injury in vivo and in vitro  [Not invited]
    Osamu Ichii, Huiyan Lu, Hideko Takahashi, Patricia Zerfas, Jeffrey Kopp
    Kidney week 2013, American Society of Nephrology  2013/09
  • 腎臓病のmicroRNA解析―動物種共通のバイオマーカー開発を目指して―  [Not invited]
    市居 修, 大塚沙織, 中村鉄平, 堀野太郎, 昆 泰寛
    第6回日本獣医腎泌尿器学会学術集会  2013/08
  • 糸球体腎炎モデルマウスの足細胞傷害 - Toll-like receptor ファミリーの関与  [Not invited]
    木村純平, 市居 修, 大塚沙織, 昆 泰寛
    第6回日本獣医腎泌尿器学会学術集会  2013/08
  • 糸球体病変を制御するmiRNAの探索−動物種共通のバイオマーカー開発を目指して−  [Not invited]
    市居 修, 大塚沙織, 中村鉄平, 野元由佳, 橋本善春, 堀野太郎, 昆 泰寛
    第155回 日本獣医学会学術集会  2013/03
  • 糸球体腎炎モデルマウスにおける足細胞傷害の解析  [Not invited]
    木村純平, 市居 修, 大塚沙織, 佐々木隼人, 橋本善春, 昆 泰寛
    第155回 日本獣医学会学術集会  2013/03
  • 熱ショック誘導性の精細管腔内石灰沈着の発生機序と抑制因子の解析  [Not invited]
    千原正尚, 市居 修, 大塚沙織, 橋本善春, 昆 泰寛
    第155回 日本獣医学会学術集会  2013/03
  • MRLマウス肥満細胞は新生子期の卵形成に関与する  [Not invited]
    中村鉄平, 市居 修, 大塚沙織, 坂田侑子, 長崎健一, 橋本善春, 昆 泰寛
    第155回 日本獣医学会学術集会  2013/03
  • Initiation of meiosis in fetal testis of MRL mouse to produce testicular oocyte  [Not invited]
    Saori Otsuka, Osamu Ichii, Nobuya Sasaki, Yoshiharu Hashimoto, Yasuhiro Kon
    第4回アジア獣医解剖学会  2012/10
  • Mast cells in neonatal ovary -a new unique phenotype of MRL/MpJ mice-  [Not invited]
    Teppei NAKAMURA, Yuko SAKATA, S. Saori OTSUKA, Osamu ICHII, Kenichi NAGASAKI, Yoshiharu HASHIMOTO, Yasuhiro KON
    第4回アジア獣医解剖学会  2012/09
  • Analysis of claudin-3 expression and function during the murine spermatogenesis.  [Not invited]
    Masataka CHIHARA, Saori OTSUKA, Osamu ICHII, Yoshiharu HASHIMOTO, Yasuhiro KON
    第4回アジア獣医解剖学会  2012/09
  • 尿毒症物質インドキシル硫酸は腎糸球体上皮細胞傷害に関与する―芳香族炭化水素受容体のリガンド作用―  [Not invited]
    市居 修, 若新 英史, 村上 太一, 堀野 太郎, Huiyan Lu, Hideko Takahashi, Zerfas Patricia, 大塚 沙織, 橋本 善春, 昆 泰寛, Jeffrey Kopp
    第154回 日本獣医学会学術集会  2012/09
  • 高温曝露後の精巣における減数分裂の進行と精細管腔内に出現する石灰沈着  [Not invited]
    千原 正尚, 市居 修, 大塚 沙織, 橋本 善春, 昆 泰寛
    第154回 日本獣医学会学術集会  2012/09
  • マレック病感染鶏由腫瘍病変部における免疫抑制因子PD-1/PD-L1発現の形態学的解析  [Not invited]
    村田史郎, 松山あゆみ, 伊勢崎 政美, 高崎紗蘭, 市居 修, 今内 覚, 大橋和彦
    第154回 日本獣医学会学術集会  2012/09
  • MRLマウス胎子精巣における卵細胞形成過程の解析  [Not invited]
    大塚沙織, 市居 修, 佐々木宣哉, 橋本善春, 遠藤大二, 昆 泰寛
    第58回東北・北海道連合支部学術集会  2012/08
  • Indoxyl sulfate: a uremic toxin and aryl-hydrocarbon receptor ligand that may cause podocyte injury  [Not invited]
    Osamu Ichii, Jeffrey B Kopp
    National Kidney Foundation, 21st Annual Fellows Research Forum  2012/06
  • Indoxyl sulfate: a uremic toxin and aryl-hydrocarbon receptor ligand that may cause podocyte injury  [Not invited]
    Osamu Ichii, Jeffrey Kopp
    The 7th annual NIDDK Fellows Retreat, NIH  2012/04
  • MRL/MpJマウスの卵巣内肥満細胞出現に関与する遺伝的因子の解析  [Not invited]
    中村鉄平, 坂田侑子, 大塚沙織, 市居 修, 並木由佳, 長崎健一, 橋本善春, 昆 泰寛
    第153回 日本獣医学会学術集会  2012/03
  • マウス精巣における密着結合蛋白claudin-3の局在および機能解析  [Not invited]
    千原正尚, 市居 修, 大塚沙織, 並木由佳, 池渕良洋, 橋本善春, 昆 泰寛
    第153回 日本獣医学会学術集  2012/03
  • High-Resolution Linkage Mapping of the Rat Hooded Locus  [Not invited]
    Torigoe Daisuke, Ichii Osamu, Ruihua Dang, Ohnaka Takayuki, Okano Shinya, Kon Yasuhiro, Sasaki Nobuya, Agui Takashi
    61st The American Association for Laboratory Animal Science  2011/10
  • 節足動物DNAのリボゾームRNA遺伝子ITS領域のサイズ分析による生物種同定の試み  [Not invited]
    佐藤福太郎, 遠藤大二, 吉村貴行, 伊東拓也, 長 雄一, 浅川満彦, 昆 泰寛, 市居 修, 大塚沙織, 林 正信
    第152回 日本獣医学会学術集会  2011/09
  • マウス涙腺炎における涙液を使った病態解析  [Not invited]
    小千田圭吾, 市居 修, 大塚沙織, 並木由佳, 橋本善春, 昆 泰寛
    第152回 日本獣医学会学術集会  2011/09
  • マウス心筋発生過程に出現するTUNEL陽性細胞の解析  [Not invited]
    長沼佑季, 市居 修, 大塚沙織, 並木由佳, 橋本善春, 昆 泰寛
    第152回 日本獣医学会学術集会  2011/09
  • MRLマウス新生子卵巣に出現する肥満細胞の系統差解  [Not invited]
    中村鉄平, 市居 修, 大塚沙織, 並木由佳, 坂田侑子, 長崎健一, 服部秀樹, 橋本善春, 昆 泰寛
    第152回 日本獣医学会学術集会  2011/09
  • 糸球体腎炎モデルマウスにおける尿中脱落細胞の動態解析  [Not invited]
    木村純平, 市居 修, 大塚沙織, 金澤智則, 並木由佳, 橋本善春, 昆 泰寛
    第57回 日本解剖学会 東北・北海道連合支部学術集会  2011/08
  • ラット頭巾斑責任遺伝子の同定  [Not invited]
    鳥越 大輔, 市居 修, 党 瑞華, 佐々木 宣哉, 昆 泰寛, 安居院 高志
    北海道実験動物研究会・日本実験動物技術者協会北海道支部 合同学術集会 2011  2011/07
  • 節足動物DNAのITS領域サイズ分析による生物種同定の試み  [Not invited]
    遠藤大二, 吉村貴行, 佐藤福太郎, 伊東拓也, 長 雄一, 浅川満彦, 昆 泰寛, 市居 修, 大塚沙織, 林 正信
    第151回 日本獣医学会学術集会  2011/03
  • 腎症候性出血熱の致死的感染モデルの開発とその病態解析  [Not invited]
    瀬戸隆弘, 吉川佳佑, 真田崇弘, Ngonda Saasa, 尾崎由佳, 市居 修, 好井健太朗, 昆 泰寛, 苅和宏明
    第151回 日本獣医学会学術集会  2011/03
  • MRL/MpJマウスにおける卵巣網由来卵巣?腫の経時的観察  [Not invited]
    李 愼曉, 市居 修, 大塚沙織, 橋本善春, 昆 泰寛
    第151回 日本獣医学会学術集会  2011/03
  • MRLマウス新生子卵巣における肥満細胞の出現  [Not invited]
    中村鉄平, 市居 修, 大塚沙織, 並木由佳, 長崎健一, 服部秀樹, 橋本善春, 昆 泰寛
    第151回 日本獣医学会学術集会  2011/03
  • 129+Ter/Svマウスの遺伝的背景は腎糸球体硬化症に抵抗性である  [Not invited]
    西野智博, 佐々木宣哉, 長崎健一, 市居 修, 昆 泰寛, 安居院高志
    第151回 日本獣医学会学術集  2011/03
  • 慢性腎臓病におけるmicroRNAの発現解析−腎間質病変に関与するmiR-146a−  [Not invited]
    市居 修, 大塚沙織, 並木由佳, 佐々木宣哉, 橋本善春, 遠藤大二, 昆 泰寛
    第151回 日本獣医学会学術集会  2011
  • マウス血液精巣関門関連分子の局在と動態 ―claudin-3, -11, occludin, ZO-1の発現解析  [Not invited]
    千原正尚, 市居修, 大塚沙織, 橋本善春, 昆泰寛
    第56回日本解剖学会 東北・北海道連合支部学術集会  2010/09
  • MRLマウスの精巣内卵細胞出現に関与する遺伝的因子の解析  [Not invited]
    大塚沙織, 市居 修, 佐々木宣哉, 並木 由佳, 橋本善春, 遠藤大二, 昆 泰寛
    第150回 日本獣医学会学術集会  2010/09
  • 尿中脱落細胞の動態は腎疾患の増悪と相関する‐糸球体腎炎モデルの解析  [Not invited]
    木村純平, 市居 修, 大塚沙織, 金澤智則, 並木由佳, 橋本善春, 昆 泰寛
    第150回 日本獣医学会学術集会  2010/09
  • Comparative analysis of the expression of aquaporin family between pre- and post-weaning periods in goat major salivary glands  [Not invited]
    Elewa Yaser, 市居 修, 大塚沙織, 金澤智則, 李 愼曉, 並木由佳, 昆 泰寛, 橋本善春
    第150回 日本獣医学会学術集会  2010/09
  • 慢性腎臓病における糸球体上皮細胞傷害の解析―腎機能とスリット膜関連分子の動態はイヌとネコで異なる―  [Not invited]
    市居 修, 矢吹 映, 佐々木宣哉, 大塚沙織, 大田 寛, 山崎真大, 滝口満喜, 並木由佳, 橋本善春, 遠藤大二, 昆 泰寛
    第3回 日本獣医泌尿器学会学術集会  2010/07
  • MRLマウス胎子精巣内における減数分裂開始と精巣内卵細胞の出現  [Not invited]
    大塚沙織, 市居 修, 佐々木宣哉, 橋本善春, 遠藤大二, 昆 泰寛
    第149回 日本獣医学会学術集会  2010/03
  • Age related structural changes of parotid salivaly glands in goat  [Not invited]
    Yaser Elewa, 橋本善春, 市居 修, 大塚沙織, 金澤智則, 昆 泰寛
    第149回 日本獣医学会学術集会  2010/03
  • マウスのネフロン形成過程における間葉‐上皮転換(MET)の解  [Not invited]
    金澤智則, 大塚沙織, 市居 修, 橋本善春, 昆 泰寛
    第149回 日本獣医学会学術集  2010/03
  • Pathological differences between dog and cat in renal disease -slit membrane molecules and renal dysfucntion-  [Not invited]
    149th Meeting of the Japanease Society of Veterinary Science  2010
  • DBA/2マウスの腎臓における遠位尿細管上皮傷害 -多発性嚢胞腎の早期病変としての可能性-  [Not invited]
    市居 修, 大塚沙織, 矢吹 映, 佐々木宣哉, 並木由佳, 橋本善春, 遠藤大二, 昆 泰寛
    第150回 日本獣医学会学術集会  2010
  • イヌおよびネコの腎疾患における病態差 −腎機能とスリット膜関連分子の動態−  [Not invited]
    市居 修, 佐々木宣哉, 矢吹 映, 大田 寛, 滝口満喜, 大塚沙織, 橋本善春, 遠藤大二, 昆 泰寛
    第149回日本獣医学会学術集会  2010
  • マウス精子形成過程における血液精巣関門構成分子の動態  [Not invited]
    千原正尚, 市居修, 大塚沙織, 橋本善春, 昆 泰寛
    平成21年度 日本顕微鏡学会 北海道支部学術講演会  2009/12
  • MRL/MpJマウスに出現する精巣内卵細胞の解析  [Not invited]
    大塚沙織, 市居 修, 佐々木宣哉, 橋本善春, 遠藤大二, 昆 泰寛
    平成21年度 日本顕微鏡学会  2009/12
  • Age-related structural changes of parotid salivary glands in goat.  [Not invited]
    Elewa Y, Ichii O, Otsuka S, Kanazawa T, Kon Y, Hashimoto Y
    平成21年度 日本顕微鏡学会  2009/12
  • Quantitative trait loci analysis of development of ovarian cyst originated from rete ovarii  [Not invited]
    李 愼曉, 市居 修, 大塚沙織, 橋本善春, 昆 泰寛
    第3回 アジア獣医解剖学会  2009/11
  • マウス精子形成過程における血液精巣関門構成分子の動態  [Not invited]
    千原正尚, 大塚沙織, 市居 修, 橋本善春, 昆 泰寛
    第148回 日本獣医学会学術集会  2009/11
  • Development of innovative method for diagnosis renal disease - Analysis of urinary cells in model mice -  [Not invited]
    木村純平, 市居 修, 大塚沙織, 橋本善春, 昆 泰寛
    Hokkaido University International Symposium on Sustainability Weeks 2009  2009/11
  • MRL/MpJマウスに見られる卵巣網由来卵巣嚢腫の量的形質遺伝子座解析  [Not invited]
    李 愼曉, 市居 修, 大塚沙織, 橋本善春, 昆 泰寛
    第147回 日本獣医学会学術集会  2009/04
  • Hydronephrosis in (C57BL/6 x DBA/2) mice  [Not invited]
    148th Meeting of the Japanease Society of Veterinary Science  2009
  • New diagnosis method for renal disease -Interleukin 1 family member 6 is a biomarker for tubular injury-  [Not invited]
    147th Meeting of the Japanease Society of Veterinary Science  2009
  • (DBA/2 x C57BL/6) F2交雑マウスに出現する水腎症  [Not invited]
    市居 修, 昆 泰寛, 佐々木宣哉, 矢吹 映, 大塚沙織, 橋本善春, 遠藤大二
    第148回日本獣医学会学術集会  2009
  • 腎疾患の新しい診断指標 −Interleukin 1 family, member 6は尿細管傷害マーカーになり得る  [Not invited]
    市居 修, 大塚沙織, 佐々木宣哉, 矢吹 映, 大田 寛, 滝口満喜, 橋本善春, 遠藤大二, 昆 泰寛
    第147回日本獣医学会学術集会  2009
  • テンシン2遺伝子の糸球体上皮細胞における機能解析  [Not invited]
    佐々木宣哉, 市居 修, 昆 泰寛, 安居院高志
    第146回 日本獣医学術集会  2008/09
  • The relations between autoimmune glomerulonephritis and Interferon activated gene 200 (Ifi200).  [Not invited]
    146th Meeting of the Japanease Society of Veterinary Science  2008
  • The effects of gonadectomy on the pathogenesis of glomerulonephritis.  [Not invited]
    145th Meeting of the Japanease Society of Veterinary Science  2008
  • Interferon activated gene 200 (Ifi200)遺伝子群と自己免疫性糸球体腎炎の関連性  [Not invited]
    市居修, 上川昭博, 佐々木宣哉, 今野明弘, 遠藤大二, 橋本善春, 昆 泰寛
    第146回日本獣医学会学術集会  2008
  • 性腺摘出が自己免疫性糸球体腎炎の病態に与える影響について  [Not invited]
    市居 修, 今野明弘, 佐々木宣哉, 遠藤大二, 橋本善春, 昆 泰寛
    第145回日本獣医学会学術集会  2008
  • The relations between autoimmune glomerulonephritis and Fc gamma receptor III(FcγRIII).  [Not invited]
    144th Meeting of the Japanease Society of Veterinary Science  2007
  • 自己免疫性糸球体腎炎と Fc gamma receptor III(FcγRIII)の関連性について  [Not invited]
    市居 修, 今野明弘, 佐々木宣哉, 遠藤大二, 橋本善春, 昆 泰寛
    第144回日本獣医学会学術集会  2007
  • Autoimmune glomerulonephritis in MRL-derived congenic mice.  [Not invited]
    142th Meeting of the Japanease Society of Veterinary Science  2006
  • MRL/MpJマウス由来コンジェニックマウスに出現する自己免疫性糸球体腎炎  [Not invited]
    市居 修, 今野明弘, 橋本善春, 昆 泰寛
    第142回日本獣医学会学術集会  2006
  • Speciese-specific differences of laboratory redent kidenys- lenghts of nephrons, GFR associated factors, water channels and sodium pumps.  [Not invited]
    140th Meeting of the Japanease Society of Veterinary Science  2005
  • 齧歯目の腎臓における種差―ネフロン長,GFR調節因子,水チャネルおよびナトリウムポンプについて  [Not invited]
    市居 修, 矢吹 映, 小嶋敏慶, 松元光春, 鈴木秀作
    第140回日本獣医学会学術集会  2005
  • Speciese-specific differences of renal structures in laboratory animals.  [Not invited]
    22th Meeting of the Kyusyu Experimental Animal Research Association  2004
  • 実験動物の腎臓の種差に関する形態計測学的研究  [Not invited]
    市居 修, 矢吹 映, 小嶋敏慶, 松元光春, 鈴木秀作
    第22回九州実験動物研究会総会  2004


Awards & Honors

  • 2018/09 The Japanese Society of Veterinary Science The Japanese Society of Veterinary Science Award
     Studies on the novel marker molecules for kidney diseases and their application to clinical veterinary medicine 
    受賞者: ICHII Osamu
  • 2017/03 Kazato Research Foundation Kazato Research Encouragement Prize
    受賞者: ICHII Osamu
  • 2013/03 Japanese Association of Veterinary Anatomists Best poster award in Japanese Association of Veterinary Anatomists
    受賞者: Osamu ICHII
  • 2011/04 Leave a Nest Co.,ltd. Leave a Nest Toray award
    受賞者: Osamu ICHII
  • 2009/03 Japanese Society of Veterinary Science Veterinary Science Young Investigator Award
     腎疾患の新しい診断指標-Interleukin 1 family,member 6 は尿細管傷害マーカーになり得る- 
    受賞者: Osamu ICHII
  • 2009/03 Japanese Society of Veterinary Science Award from the chairman
     腎疾患の新しい診断指標-Interleukin 1 family,member 6 は尿細管傷害マーカーになり得る- 
    受賞者: Osamu ICHII
  • 2008/03 Japanese Association of Veterinary Anatomists Best presentation award in Japanese Association of Veterinary Anatomists
    受賞者: Osamu ICHII
  • 2007/09 Japanese Association of Veterinary Anatomists Award in Japanese Association of Veterinary Anatomists
     自己免疫性糸球体腎炎とFc gamma receptor III (Fcgr3)の関連性について 
    受賞者: Osamu ICHII

Research Grants & Projects

  • イヌの新規ゲノムワイドDNAメチル化解析:腫瘍性疾患特異的DNAメチル化の同定
    Date (from‐to) : 2018/04 -2021/03 
    Author : 山崎 淳平
  • 体液顕微解剖の実践:原尿中エクソソーム由来マイクロRNAに腎障害マーカーを求めて
    Date (from‐to) : 2018/04 -2021/03 
    Author : 市居 修
  • ウシの各種感染性疾患におけるバイオフィルムの機能解析
    Date (from‐to) : 2017/06 -2019/03 
    Author : 市居 修
  • 産業動物の粘膜関連リンパ組織の探索―より効果的なワクチン接種部位を求めて―
    公益財団法人 伊藤記念財団:研究助成
    Date (from‐to) : 2017/06 -2019/03 
    Author : 市居 修
  • 走査型電子顕微鏡の応用的手法による腎臓病理解析法の革新
    Kazato Research Foundation:Kazato Research Encouragement Prize
    Date (from‐to) : 2017/04 -2019/03 
    Author : ICHII Osamu
  • 新たなlgA腎症モデル動物の発見とその病態解析-カスパーゼ3の原因遺伝子としての役割-
    株式会社ケー・エー・シー:創立40周年記念 研究助成
    Date (from‐to) : 2018/04 
    Author : 市居 修
  • 文部科学省:科学研究費補助金(若手研究(A))
    Date (from‐to) : 2015 -2017 
    Author : 市居 修
  • 文部科学省:科学研究費補助金(挑戦的萌芽研究)
    Date (from‐to) : 2015 -2016 
    Author : 市居 修
  • 文部科学省:科学研究費補助金(若手研究(A))
    Date (from‐to) : 2012 -2012 
    Author : 市居 修
    本研究では、短鎖のRNA(micorRNA ; miRNA)をバイオマーカーとして獣医学に応用することを目的としている。対象疾患としては、伴侶動物で急増する慢性腎臓病に着目した。本年度はバイオマーカーmiRNA候補選抜のため、慢性糸球体腎炎(GN)モデルマウス(B6.MRLc1)を主に解析した。GNマウスは膜性増殖性糸球体腎炎を発症し、メサンギウム増殖、糸球体基底膜の二重化・免疫複合体沈着、足細胞傷害、糸球体でスリット膜関連分子の発現低下ならびに炎症メディエーターの発現増強等を示す。GNマウスの糸球体を分離し、健常マウスとのmiRNAマイクロアレイ比較解析を実施した。4種のmiRNA(miR-92b*、let-7a、miR-26a、miR-195)がGNマウスの病態初期に有意に変動するmiRNAとして同定された。特に、1et-7a、miR-26a、およびmiR-195は健常マウスの糸球体に強く発現し、GNマウスでその発現は低下することをTaqManPCRで明らかにした。miRNAの発現局在をin situ hybridization法で解析し、糸球体構成細胞に陽性シグナルが得られた。さらに、let-7a、miR-26a、およびmiR-195はイヌ、ネコ、ウシ、およびウマの糸球体にも発現することを明らかにした。これらmiRNAは尿に出現し、尿沈渣を除いた尿上清からも検出され、GNモデルにおける1et-7a、miR-26a、およびmiR-195の尿中miRNAレベルは低値だった。in vitro解析において、miR-26aは足細胞株、miR-195はメサンギウム細胞株に強く発現し、特に前者は足細胞の分化と共に発現上昇を示した。足細胞をLPSで傷害したところ、アクチンの減少やCell Viabilityの低下と共に細胞内miR-26a発現も低下した。一方で、LPS刺激中、培養上清中miR-26aレベルは一過性に上昇し、後に減少した。本年度の研究において、糸球体特異的かつ動物種に共通して発現し、さらには尿で検出しうるバイオマーカー候補miRNAを選抜した。特に、糸球体内miR-26aの発現変化は足細胞傷害と関連があり、その尿中検出は非侵襲的な糸球体病変の把握に繋がると考えられる。今後、今回同定したバイオマーカーmiRNA候補さらには新規候補についてマウス以外の動物種でも検討していく。
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 2010 -2012 
    Author : Akira YABUKI, 大和 修, 市居 修, 保坂 善真, 水上 圭二郎, 美谷沙 和音, 富永な おみ
    In the present study, we investigated pathological mechanisms of kidney diseases in dogs and cats, especially involvement of cyclooxygenase (COX) and renin-angiotensin (RA) system. Results from pathological investigation demonstrated close and complicated relationships between renal COX and RA system and progression of the kidney diseases, and such mechanisms were clearly differentbetween dogs and cats. Investigation using model mice demonstrated the renoprotective effect of piroxicam (COX inhibitor), and it was suggested that such renoprotective effect was induced from the downregulation of TGF-beta.
  • 種の壁を越えた尿中microRNAバイオマーカーの開発-慢性腎臓病の非侵襲的早期診断法への応用-
    Date (from‐to) : 2012 
    Author : 市居 修
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(若手研究(スタートアップ), 研究活動スタート支援)
    Date (from‐to) : 2009 -2010 
    Author : Osamu ICHII
    This study clarified that the renal parenchymal cells were dropped into urine in renal pathological conditions. The quantitative and qualitative urinary cellular patterns correlated with the deteriorations of renal pathology and function in renal disease models and companion animals. Importantly, these urinary cells could be detected by molecular biological methods targeting mRNA and microRNA in urine. These data indicated the possibility that the urinary tests based on the detections of urinary cells, entitled "Urinary Molecular Profiling" in the present study, could be noninvasive diagnos...
  • 自己免疫性糸球体腎炎モデルの解析
    Date (from‐to) : 2007 -2008 
    Author : 市居 修
  • Development of neo-biomarker for renal disease
    Grant-in-Aid for Scientific Research
    Date (from‐to) : 2008
  • Research of autoimmune glomerulonephritis
    Grant-in-Aid for Scientific Research
    Date (from‐to) : 2005

Educational Activities

Teaching Experience

  • 獣医科学・感染症学基礎科目 研究機器演習
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 国際感染症学院
  • Practice in Histology
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 顕微鏡、細胞、上皮組織、結合組織、支持組織、筋組織、神経組織、消化器系、呼吸器系、尿生殖器系、内分泌系、免疫系、神経系、感覚器、外皮、鳥類組織学、免疫組織学、超微形態学
  • 獣医科学基礎科目B 研究機器演習
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • Anatomy
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 骨学、筋学、脈管学、神経学、内臓学、肉眼解剖学、解剖学用語
  • 先端獣医科学特論B 生命科学特論Ⅳ:発生生物工学
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学研究科
  • Freshman Seminar
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : 動物、器官、臓器、組織、構造、細胞、発生
  • 獣医科学基礎科目 研究機器演習
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • Embryology
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 発生生物学、モデル動物、前発生、始原生殖細胞、卵割、着床、胎膜(卵黄嚢、栄養膜、羊膜、尿膜、絨毛膜、胎盤)、外胚葉、中胚葉、内胚葉、神経管、神経堤、心内膜筒、心ループ、心内膜隆起、大動脈弓、主静脈、卵黄嚢静脈、臍静脈、咽頭弓、前腸、中腸、後腸、中腎管、中腎傍管、尿管芽、生殖索、膜性骨化、軟骨性骨化
  • 獣医科学基礎科目 生命科学特論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • Histology
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 細胞、上皮組織、結合組織、支持組織、筋組織、神経組織、消化器系、呼吸器系、尿生殖器系、内分泌系、免疫系、神経系、感覚器、外皮、鳥類組織学
  • 先端獣医科学科目 先端生命科学特論Ⅰ:発生生物学
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • Practice in Anatomy
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 骨学、筋学、脈管学、神経学、内臓学、肉眼解剖学、解剖学用語
  • アドバンスト演習
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 獣医学部

Social Contribution

Social Contribution

Social Contribution

  • 肉眼動物解剖技術研修会
    Date (from-to) : 2016/09-Today
    Role : Lecturer
    Sponser, Organizer, Publisher  : 日本獣医解剖学会
  • 日本獣医解剖学会組織標本ライブラリー(HistoJAVA)・庶務担当
    Date (from-to) : 2015/04-Today
    Role : Planner
    Sponser, Organizer, Publisher  : 日本獣医解剖学会
  • 理系応援キャラバン隊
    Date (from-to) : 2016/07
    Role : Organizing member
    Sponser, Organizer, Publisher  : 北海道大学 人材育成本部

Academic Contribution

  • NISTEP専門調査員
    Date (from-to) :2017/04-Today
    Role: Academic research planning
    Type: Academic research
    Organizer, responsible person: 科学技術予測センター

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